Cleome rutidosperma DC. (commonly known as Nil Hurhure) and Pouzolzia zeylanica (L.) Benn. (locally referred to as Kulluruki) are two medicinal plants widely found in various regions of Bangladesh. Cleome rutidosperma, a low-growing herb of the Capparidaceae family, typically reaches a height of up to 70 cm and is found in areas such as Chittagong. Pouzolzia zeylanica, a perennial herb from the Urticaceae family, is widely distributed across Bangladesh, particularly in tribal regions like Bandarban, Chattogram, Cox's Bazar, Khagrachhari, and Rangamati. Both plants have been used in traditional herbal medicine for their wide range of pharmacological benefits in treating various diseases. In this study, the methanolic extracts of powdered leaves of Cleome rutidosperma and Pouzolzia zeylanica were tested for their thrombolytic potential using human erythrocytes. The results revealed that Cleome rutidosperma exhibited a clot lysis of 22.96±2.12%, while Pouzolzia zeylanica showed 36.15±1.51% clot lysis. Whereas, the sterile distilled water (negative control) and streptokinase (positive control) demonstrated clot lysis of 4.9±0.59% and 81.67±2.62%, respectively. The observed thrombolytic activity may be attributed to the presence of phytochemical compounds, such as tannins, alkaloids, and saponins, in the plant extracts. Although no previous research has specifically examined the thrombolytic potential of Cleome rutidosperma and Pouzolzia zeylanica, our findings suggest that the clot lysis effect of both plants is noteworthy when compared to the positive control and negative control. Based on these results, we propose that the methanolic leaf extracts of Cleome rutidosperma and Pouzolzia zeylanica possess moderate thrombolytic potential, making them promising candidates for future drug development.