A series of piperine analogs were synthesized by the condensation of piperic acid with different amino acids and substituted aniline. The synthesized compounds (4a–4e) were evaluated for their anticancer activity against human cancer cell lines (MCF-7, Breast Cancer cell line, and Hela cervix cell line) and antibacterial activity against human pathogens (Escherichia coli, Klebsiella pneumoniae, Salmonella typhi, Shigella dysenteriae, Bacillus subtilis, Staphylococcus aureus, Pseudomonas aeruginosa). The efficacies of the synthesized compounds were superior to those of piperine in all tested human cancer cell lines. Among the tested conjugates, 4c showed significant anticancer activity against Hela cervix cell line with IC50 of 0.736 μmol and 4a showed significant activity against breast cancer cell line. The antibacterial activity of the tested compounds was also found to be superior to that of piperine. The approach is novel as the abundantly available natural product piperine is utilized as precursor for the synthesis of new potential antimicrobial and anticancer agents.