Background Thyroid cancer is a malignancy that arises from the thyroid gland. While it is considered an uncommon condition, cases of thyroid cancer have been steadily rising in recent years worldwide.Purpose The present work assesses the apoptotic-inducing potential of diosmetin against thyroid cancer cells.Materials and Methods he impact of diosmetin on the growth of cells was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test. Apoptosis in the experimental CAL-62 cells was assessed using dual staining and 4 ',6-diamidino-2-phenylindole (DAPI) staining. Oxidative stress marker levels were quantified in the cell lysates of CAL-62 cells exposed to diosmetin. PI3K/AKT/mTOR signaling protein levels were also assessed using cell lysates from both control and diosmetin-treated CAL-62 cells.Results The present results exhibited that diosmetin efficiently decreased the viability of both CAL-62 and BHT-101 cells. Additionally, diosmetin considerably induced apoptosis in CAL-62 cells, as evidenced by the fluorescent staining assay results. Diosmetin treatment remarkably increased TBA reactive species (TBARS) levels and subsequently decreased anti-oxidant levels in CAL-62 cells. Moreover, diosmetin treatment effectively blocked PI3K/AKT/mTOR signaling in CAL-62 cells.Conclusion The findings of this work exhibit that diosmetin efficiently inhibits cell proliferation and promotes oxidative stress-mediated apoptosis in thyroid cancer CAL-62 cells. Consequently, it possesses the potential to serve as an anti-cancer agent in treating thyroid cancer.