Sesamol is a strong antioxidant phenolic compound found in sesame seed. It possesses the ability to scavenge intracellular reactive oxygen species (ROS) and to inhibit malic enzyme activity and NADPH supply, resulting possibly in cell proliferation and alteration in the fatty acid composition. In the present study, the effect of sesamol on the growth and accumulation of docosahexaenoic acid (DHA) was investigated in the marine microalga Crypthecodinium cohnii, a prolific producer of DHA. C. cohnii showed a great decrease in the intracellular ROS level with the addition of sesamol. In contrast, the biomass concentration, DHA content (% of total fatty acids), and DHA productivity were significantly increased by 44.20, 11.25, and 20.00%, respectively (P < 0.01). Taken together, this work represents the first report of employing sesamol for enhanced production of DHA by C. cohnii, providing valuable insights into this alga for future biotechnological applications.