Paullinia pinnata L. (Sapindaceae) is widely used ethnomedicinally in Ghana for the treatment of wounds and other skin diseases. In this study, the in vivo effect of the methanolic extract of P. pinnata on incision and excision wound models in rats were investigated, as well as the in vitro cytoprotective action of the extract on 142BR cell line against hydrogen peroxide-induced damage. The results of the in vivo wound healing tests showed that, upon administration of P. pinnata ointment, there was a decrease in the epithelialization period from 26.7 days (control) to 12.7 days along with a marked decrease in the scar area of 54.2 mm2 (control) to 26.2 mm2. There was also a significant increase in the tensile strength and hydroxyproline content compared to the control and comparable to nitrofurazone. The percentage closure of excision wound area showed that P. pinnata extract significantly stimulated wound contraction up to 69.2% in 7 days as compared to 46.2% given by the control and 67.5% by nitrofurazone. The in vitro cytoprotective studies revealed that different concentrations of the extract, applied simultaneously with 10−4M hydrogen peroxide in the growth medium protected the human dermal fibroblast cells (142BR) against hydrogen peroxide-induced damage, the maximum being 86% at 50 μg/ml, almost comparable with that of catalase (control at 250 units/ml).