The main differences between a macromolecule and small molecules are:
Macromolecules usually have a much higher molecular weight.
They may have complex, three-dimensional structures and important functions for cellular life. For example, nucleic acids encode genetic information, and proteins catalyze chemical reactions.
They have variable physical and chemical properties. While small molecules have fixed, limited properties, macromolecules may change shape or structure in response to external or internal stimuli. In the case of nucleic acids and genetic information, this enables the mutations involved in natural selection, for example.