Short-chain fatty acids are organic acids manufactured by the gut microbiota. The type and amount of microflora in the colon, the source of substrate and the transition period through the intestine affect the rate and amount of Short-chain fatty acids production. Ferrostatin-1, a synthetic compound and a potent inhibitor of ferroptosis, is an antioxidant capable of inhibiting ferroptosis. Paclitaxel is a type of chemotherapy called taxane and causes peripheral neuropathy as a side effect of cancer treatment. In this study, we researched the effect of paclitaxel and ferrostatin-1 administration on fecal Short chain fatty acids. For this purpose, rats were divided into four groups as control (n = 6), paclitaxel (n = 8), ferrostatin (n = 9) and paclitaxel + ferrostatin (n = 9). Paclitaxel (10 mg/kg) and ferrostatin-1 (5 mg/kg) were administered intraperitoneally once a week for 4 weeks. At the end of the experiment, the amounts of Short-chain fatty acids (acetate, propionate and butyrate) and branched-chain fatty acids (iso-butyrate and iso-valerate) in the feces were determined by gas chromatography. According to the results obtained, acetate level increased significantly (P < 0.05) in Ferrostatin-1 treated group compared to control group and total Short-chain fatty acids level increased significantly (P < 0.05) in Ferrostatin-1group compared to Ferrostatin-1 + Paclitaxel group. Although statistically insignificant, it was observed that ferrostatin-1 increased all the Short-chain fatty acids except butyrate, while paclitaxel decreased all the Short-chain fatty acids. The findings of this study suggest that ferrostatin-1 and paclitaxel may affect the functions of microorganisms in the large intestine and thus the amount of microbial Short-chain fatty acids. In addition, it is clear that therapeutic targeting of these specific bacteria, and thus the produced Short-chain fatty acids, will be important for successful treatment regimens and improved quality of life, especially in cancer patients, and may improve treatment outcomes.