Bisphenol A (BPA) and octylphenol (OP) are industrial chemicals used in the manufacture of polycarbonate plastics, epoxy resins, and non-ionic surfactants. In the present study, we investigated the possible in vivo genotoxic effects of these compounds in rats using single-cell gel electrophoresis, the so-called comet assay. Adult male Wistar albino rats were divided randomly into six groups as follows: BPA125 (received 125 mg/kg bw BPA; n = 6), OP125 (received 125 mg/kg bw OP; n = 6), BPA250 (received 250 mg/kg BPA; n = 6), OP250 (received 250 mg/kg bw OP; n = 6), control (n = 5), and MMS (positive control group that received methyl methanesulfonate; n = 3). Both BPA and OP were orally administrated for 4 weeks. Controls were orally inoculated with corn oil for 4 weeks as well. Comet parameters including tail length and tail moment were evaluated for possible genotoxic effects. There were no significant differences in the OP125 and in the BPA125 compared with the control group, regarding tail length and tail moment (P > 0.05). However, there were significant differences in the OP250 and in the BPA250 compared with the control group, regarding tail length and tail moment (P < 0.05 and P < 0.01, respectively). The genotoxic potential of BPA and OP was investigated in vivo; there is a need for further studies exploring further mechanisms of the genotoxic potential of these chemicals in vivo.