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The study was intended to compare and evaluate the in vitro thrombolytic activity and in vivo anxiolytic activities of methanol extracts of Piper nigrum fruits (MEPNF) and Sesamum indicum seeds (MESIS). An in vitro thrombolytic activity was employed by investigating the clot lysis effect of MEPNF, MESIS, and their combinations. In vivo anxiolytic activity of MEPNF and MESIS was examined by using the Elevated Plus Maze (EPM) test considering diazepam (1 mg/kg) as the standard drug. In the thrombolytic test, MEPNF and MESIS showed a moderate (P< 0.01) clot lysis activity. Besides, MEPNF and MESIS showed significant (P< 0.001) dose-dependent anxiolytic activity. Since MEPNF or MESIS 200 and 400 (mg/kg, bw; po) has been administered, the time spent in the open arms, and the number of entry into the open arms were increased. The finding suggests that MEPNF and MESIS may be the source for biological activity and therefore further research is required for confirmation.