###### Abstract  
Corn silk, derived from the stigmas of corn (_Zea mays_, Poaceae) flowers, possesses valuable bioactive compounds that can be harnessed for therapeutical, nutritional, and industrial purposes. This research aimed to optimize the extraction of bioactive compounds from corn silk, specifically flavonoids and total antioxidant capacity, by comparing it with classical extraction (infusion and maceration). The study identified significant factors influencing total flavonoid content (TFC) and antioxidant activity (assessed through an ABTS assay), including ethanol concentration, ultrasonic amplitude, and their quadratic interactions. This optimized combination of independent variables (37.89% ethanolic concentration, 48.58% ultrasound amplitude, and an extraction time of 38.72 min) yielded a balanced extraction, maximizing both TFC and antioxidant activity. Further analyses revealed significant total phenolic content, total flavonoid content (50.69 \(\pm\) 0.36 mg GAE, 23.54 \(\pm\) 0.01 mg QE, and 78.33 \(\pm\) 0.94 mg TE/g extract, respectively), and potent in vitro antioxidant activity, affirming the efficacy of the optimized extraction. The study also explored the inhibitory effects on \(\alpha\)-glucosidase (IC50 = 411.67 \(\pm\) 25.39 \(\mu\)g/mL), acetylcholinesteraseinesterase (IC50 = 1166.4 \(\pm\) 399.38 \(\mu\)g/mL), and pancreatic lipase (IC50 = 1519.67 \(\pm\) 209.04 \(\mu\)g/mL), showcasing potential antidiabetic and neuroprotective properties. While tyrosinase inhibition activity was not observed, the research emphasizes the nutraceuticalital potential of corn silk, offering valuable insights for its utilization and further exploration in the pharmaceutical and functional food industries. Maymetric tons [1]. On the other hand, according to Eurostat, the EU produced 270.9 million tons of cereals in 2022, of which 53 million tons were corn [2]. CS has long been known as a valuable herb, especially by the earliest human populations that started harvesting it, i.e., the Cherokee and Navajo native American tribes. These ancient tribes once used CS for infectious diseases, cardiovascular ailments, and urological problems [3]. Once corn began to spread worldwide through European colonialists, CS started to be used as a fair pain relierer for afflictions encountered in the renal pathological sphere, such as kidney stones, urinary tract infections (UTIs) or edema, and also in obesity [4]. The chemical composition of corn silk reveals a complex mixture of bioactive compounds that contribute to its medicinal properties. Various studies have aimed to identify and characterize these compounds, shedding light on the potential therapeutic effects of corn silk. Some of the key chemical constituents found in CS include flavonoids (CSF), such as quercetin, kaempfer, and rutin [5]. Corn silk is identified as an excellent source of flavuces. Two novel flavuces glycosides from corn silk are identified as 2\({}^{\prime\prime}\)-O-\(\alpha\)-L-rhammosyl-6-C-3\({}^{\prime\prime}\)-deoxyglucosyl-3\({}^{\prime}\)-methoxyluteolin and 6,4\({}^{\prime}\)-dihydroxy-3\({}^{\prime}\)-methoxyflavuce-7-O-glucose through spectral analyses [6]. Moreover, two flavuce glycosides, issoorientin-2\({}^{\prime\prime}\)-O-\(\alpha\)-L-rhammoside and 3\({}^{\prime}\)-methoxysmin, were isolated from the \(n\)-butanol fraction [7]. The results suggest that corn silk extracts, especially the flavuce glycosides, have the potential to serve as a valuable and readily accessible bioactive source of natural antioxidants. CS has recently attracted worldwide attention from the scientific community, as there have been numerous articles published in the last ten to twenty years. These studies describe novel molecules found in the plant matrix that may be linked to the various types of CS. CS's diuretic properties are the most known and well documented in the literature. It is proven that CSF increases water excretion and has an impact on Na\({}^{+}\) and K\({}^{+}\) excretion and re-uptake [8; 9; 10].