A series of 5-substituted-4-amino-3-mercapto-1,2,4-triazoles were synthesized and were treated with various 3-substituted pyrazole aldehydes to obtain a series of new Schiff bases (3a–l). Few of the selected Schiff bases were converted into Mannich bases by reaction with diphenylamine/morpholine in presence of formaldehyde in ethanol media (4a–e, 5a–e). These newly synthesized compounds were characterized by elemental analysis, IR, NMR and mass spectrometry studies. A comparative study on the cytotoxic activities of few selected Schiff and Mannich bases was done in HepG2 cells using MTT assay. Few of the screened Schiff bases, 3a, 3d, 3e, 3g and 3h showed dose dependent cytotoxic activity, 3a being the most potent with an IC50 value of 0.018 g/l comparable to the standard drug doxorubicin. Among the Mannich bases, 5b was the most active with an IC50 value of 0.034 g/l. The Schiff bases were found to be more active, when compared to Mannich bases derived from them. The morpholine derived Mannich bases were more potent than those obtained from diphenyl amine.