Novel piperamide bearing 4-hydroxypiperidine as antidepressant and antioxidant agent. A series of piperamide derivatives (8a–j) was synthesized with various substituted piperidine and piperazine compounds. The prepared compounds were evaluated for antibacterial activity against gram-positive and gram-negative bacteria and antifungal activity by disc diffusion method. The antioxidant activity of the compounds was evaluated by DPPH and superoxide radical scavenging method and antidepressant activity using forced swim and tail suspension behavioral despair tests in mice. The compounds 8a, 8b and 8c were investigated for their monoamine oxidase A and B (MAO-A and MAO-B) inhibitory property. Some of the test compounds were active in forced swim test (FST) and tail suspension test (TST). Compounds 8a and 8b showed a significant effect, when compared to standard drug, clorgyline.