Background: Black seed oil and Phytol (PHY) are evident for their promising biological effects in various test systems. Aim: This study evaluates anti-atherothrombosis activity of Nigella sativa oil (NSO) and Phytol (PHY). Materials and Methods: The clotlysis activity of the NSO and/or PHY has been investigated by taking Streptokinase (SK) as a standard clotlysis drug. Results: The results suggest that the NSO and PHY exhibited a concentration-dependent clotlysis activity in human clotted blood. The highest clotlysis of the NSO and PHY was seen by 57.83 ± 0.23% and 53.05 ± 2.93% with 80 μL and 150 μg per tube, respectively. NSO co-treated with PHY showed a better clotlysis capacity than the NSO and PHY. The vehicle showed negligible clotlysis (2.86 ± 4.33%) capacity, while the standard SK (100 I.U.) showed 78.96 ± 1.08% clotlysis activity. Conclusion: NSO and/or PHY exhibited clotlysis activity in human clotted blood in in vitro.