Over the past twenty years (1998-2023), extensive research has focused on the synthesis and biological activity of Mannich base derivatives of flavonoids (FMBD), which have demonstrated exceptional properties towards organic and bioorganic molecules. Several research groups have reported the pharmacological potential of these flavonoid derivatives, including antioxidant and antiviral activities, as well as their ability to inhibit AChE and exhibit anticancer properties. Moreover, the unique characteristic of forming stable complexes with biomolecules positions flavonoid derivatives as valuable assets in the realm of biology and drug discovery. In this extensive review, we ' ve meticulously analyzed over seventy six distinct research studies on this subject. Our aim is to provide a succinct overview of the wide-ranging applications of flavonoid derivatives coupled with amines. Furthermore, we explore the promising horizons and potential innovations in this field. It's essential to highlight that these derivatives display no discernible signs of toxicity or eliciting immune responses, making them even more attractive for biopharmaceutical applications. Undoubtedly, the utilization of flavonoid derivatives combined with amines as crucial biopharmaceutical agents is poised for significant expansion in the forthcoming years. In this comprehensive review, we have painstakingly examined more than seventy-six distinct research studies conducted on this subject from 1998 to 2023. Our extensive research has been primarily focused on the synthesis and biological activity of Mannich base derivatives of flavonoids, which have exhibited remarkable properties in interactions with both organic and bioorganic molecules. Various research teams have reported the pharmacological potential of these flavonoid derivatives, encompassing their role as antioxidants and antiviral agents, as well as their capability to inhibit AChE and demonstrate anticancer properties. Furthermore, the exceptional ability of these derivatives to form stable complexes with biomolecules positions them as invaluable assets in the fields of biology and drug discovery.image