Background: In this study, the effectiveness of dexpanthenol and coenzyme Q10 (CoQ10) on the healing of ischemic colon anastomosis was investigated. Methods: Forty eight maleWistar Albino rats were divided into four equal groups (Sham-S, Sham-I, DXP, Q10). Following full layer colon resection, single layer colon anastomosis, without creating ischemia, was performed on the Sham-S group. The same experimental model was performed on remaining groups after ischemia was created. Intraperitoneal dexpanthenol and CoQ10 was administered to the DXP and Q10 groups once a day for three days. Ten days later, all colon anastomoses were investigated histopathologically and biochemically, as well as their burst pressure values, in all sacrificed rats. Results: The highest burst pressure value was observed in the Sham-S group, decreasing from high to low in the DXP, Q10, and Sham-I groups, respectively (p = 0.008). Furthermore, tissue hydroxyproline (p = 0.001) level values were significantly different among the groups. Additionally, histopathological analysis revealed a significant difference among groups regarding reepithelization (p = 0.027) and polymorphonuclear leukocyte density (p = 0.022). Conclusions: This preliminary study has shown that ischemia-reperfusion injury may impair the healing of colon anastomosis and it has been concluded that dexpanthenol and CoQ10 may have positive effects on the healing of ischemic colon anastomosis in rat, although re-epithelization may be adversely affected using CoQ10.