Dental caries is one of the most prevalent chronic diseases in people worldwide. It results in localized dissolution and destruction of the calcified tooth tissues. The destruction of the dental structure does not occur as a result of a localized accumulation of bacteria, but rather as a result of an invasive and infectious process caused by the interaction of several interconnected factors. These factors make dental caries a great challenge for the dentist, as they seek an efficient means to control it. Carious dentin consists of two distinct layers: an outer "caries-infected dentin" and an inner "caries-affected". The "caries-affected" dentin is described as demineralized inter-tubular dentin, crystal deposition in dentinal tubules, and a lesser amount of destructed collagen matrix with no bacterial invasion. On the contrary, the "caries-infected" dentin displays deformation of the microstructure of the dentinal tubules and permanently damaged collagen fibers with significant penetration of the bacteria. Thus, the "caries-infected" dentin has to be removed only during caries removal. Traditional clinical treatment of dental decay has developed on the basis of the removal of carious tissues with high-speed handpieces and slow-rotating instruments, inducing pain, disturbing sounds, and vibrations. In addition, this method comprises the tooth structure by removing both "caries-affected dentin" and "caries-infected dentin". The concept of minimal intervention dentistry (e.g., air abrasion, laser, chemo-mechanical caries removal (CMCR) agents) includes the selective removal of caries-infected dentin while preserving the healthy caries-affected dentin that has the ability to remineralize. It is less destructive and less painful, thereby promoting a positive attitude towards visiting dentists among children. Brix Medical Science in 2016 released a new CMCR agent named "BRIX3000®". It is an enzymatic gel for non-traumatic caries removal known with exclusive technology as "Encapsulating Buffer Emulsion" (EPE) that is claimed to have superior characteristics for caries removal compared to previous products available in the dental market. There are a few studies present in the literature, most of them published in non-English language versions, evaluating the clinical and laboratory properties of "BRIX3000®". Therefore, investigations were required to evaluate and compare the outcomes of "BRIX3000®" versus the previous CMCR agent, "Carie-CareTM" and the traditional surgical methods. This study was carried out at King Abdulaziz Dental University Hospital (KADUH) and the Microbiology Research Laboratory in the Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia to evaluate the efficacy, efficiency, and pain experienced by children with the use of the CMCR agents "BRIX3000®" and "Carie-CareTM" versus the traditional surgical method in primary molars. The study was approved by the "Research Ethics committee" at the Faculty of Dentistry, King Abdulaziz University (KAU) under approval number 107-06-19. Informed written consent will be signed by the parents/guardians of the children after explaining it to them. The study sample will be consisted of healthy and cooperative children aged 4 to 9 years old with bilateral open occlusal carious lesions in primary molars who will be seen as outpatients at KADUH's Department of Pediatric Dentistry from October 2019 to December 2020.The sample size was measured using G power analysis for calculating an estimated sample size. The final sample will be consisted of 60 children aged 4-9 years with 30 pairs of matched contralateral open occlusal carious lesions in primary molars meeting the inclusion criteria. They will be randomly allocated to either group (1) or group (2). In group 1, 30 children with 60 primary molars will be subjected to caries removal by the CMCR method "BRIX3000®" (the experimental group) on one molar (n = 30) and the traditional surgical method (the control group) on the contralateral molar (n = 30). In group 2, 30 children with 60 primary molars will be subjected to caries removal by the CMCR method "Carie-CareTM" (the experimental group) on one molar (n = 30) and the traditional surgical method (the control group) on the contralateral molar (n = 30). The block randomization method (a block of the two contralateral teeth) will be used to make sure that each side was treated evenly by both methods. The statistical assessment will be carried out using the Statistical Package for Social Sciences (SPSS, V.20, IBM, NY, USA). A significance level of 5% was utilized for all analyses.