Background <p>The potential harmful effects of cancer treatments on reproductive function have now been clearly recognized. Exposure to chemotherapy is considered a risk factor for premature ovarian failure and causes infertility. This study investigated the prophylactic effects of gallic acid (GA) against cyclophosphamide (CP)-induced ovarian damage in rats.</p> Methods <p>Thirty-two adult female Sprague Dawley rats were randomly assigned into four groups (control, CP, GA, and CP + GA). No procedure was applied to the control group. The CP group received 150&#xa0;mg/kg CP via the intraperitoneal (i.p.) route on day 7 of the experiment. The GA group received 20&#xa0;mg/kg GA daily for seven days from day 1 of the experiment via oral gavage. The CP + GA received 20&#xa0;mg/kg GA daily for seven days from day 1 of the experiment via oral gavage and 150&#xa0;mg/kg i.p. CA on day 7 of the experiment. All rats were sacrificed on day 8. Sections taken from the ovaries were stained using hematoxylin-eosin, Masson’s trichrome, Periodic Acid-Schiff, and the TUNEL method. Histopathological examination of ovarian tissues and follicle counting were performed. Glutathione peroxidase (GPX), superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), tissue anti-müllerian hormone (AMH), and serum AMH levels were examined during biochemical investigation.</p> Results <p>Follicular cell degeneration increased significantly in the CP group compared to the control and GA groups (<i>p</i> &lt; 0.001 for both). Follicular cell degeneration in the CP + GA group was significantly lower than in the CP group (<i>p</i> = 0.003), but higher than in the control and GA groups (<i>p</i> = 0.005, <i>p</i> = 0.015 and <i>p</i> = 0.029, respectively). The GA and control groups exhibited similar morphologies. The apoptotic index was higher in the CP group than in the control and CP + GA groups (<i>p</i> = 0.032 and <i>p</i> = 0.032, respectively). Primordial follıcle cell numbers decreased significantly in the CP group compared to the control and CP + GA groups (<i>p</i> = 0.015 and <i>p</i> = 0.029, respectively). Unilaminar primary follicle cell numbers were lower and atretic cell numbers were higher in the CP group than in the control and GA groups (<i>p</i> &lt; 0.001 and <i>p</i> = 0.008, respectively). The numbers of unilaminar primary follicles were lower in the CP + GA group than in the control group (<i>p</i> = 0.009), while atretic follicle numbers were higher than in the control and GA groups (<i>p</i> &lt; 0.001 for both). Atretic follicle numbers were also higher in the CP + GA group than in the control and GA (<i>p</i> = 0.009 and <i>p</i> = 0.008, respectively). MDA levels were higher in the CP than in the control and GA groups (<i>p</i> = 0,003 and <i>p</i> = 0.001, respectively). MDA levels in the CP + GA decreased compared to the CP group (<i>p</i> = 0.002). SOD activity decreased in the CP group compared to the control, CP + GA, and GA groups (<i>p</i> = 0.003, <i>p</i> = 0.006 and <i>p</i> = 0.038, respectively). Tissue CAT activity was lower in the CP group than in the control group (<i>p</i> = 0.038). Tissue CAT activity increased in the CP + GA group compared to the control and CP groups (<i>p</i> &lt; 0.001 for both). Tissue CAT activity also increased in the GA group compared to the control and CP groups (<i>p</i> = 0.001 for both). Tissue AMH was lower in the CP group compared to the control group (<i>p</i> = 0.015), while serum AMH was higher in the GA group than in the other groups (<i>p</i> = 0.003, <i>p</i> = 0.003, and <i>p</i> = 0.022, respectively). No intergroup difference was observed in GPX levels.</p> Conclusions <p>GA can be effective in preventing follicle cell damage caused by CP in the ovary.</p>