Novel 1-benzhydryl piperazine derivatives 7(a-k) and 8(a-i) were synthesised in order to determine their antimicrobial activity and possible structure-activity relationships to improve the efficacy. Their chemical structures were confirmed by 1H NMR, IR and elemental analysis. All the compounds were screened for their in vitro antibacterial activity against Bacillus subtilis, Escherichia coli and Staphylococcus aureus by using Streptomycin as positive control and antifungal activity against Aspergillus niger, Cephalosporium acremonium and Fusarium moniliforme by using Nystatin as positive control. Among the synthesized novel compounds 7h, 7k, 8g, 8h and 8i showed potent antimicrobial activities compared to the standard drugs. The SAR studies reveals that, both linkage and substituents on phenyl ring are responsible for the antimicrobial activity for these class of agents.