This study aimed to investigate the anti‐inflammatory and wound healing effects of the polysaccharide extract from Opuntia ficus‐indica cladodes (TPL‐Ofi) using a rat cutaneous wound model. After anaesthesia, four 7‐mm‐diameter dorsal wounds per animal (n = 6/group for each experimental day of evaluation) were created in female Wistar rats using a surgical punch. The animals were treated topically twice daily with TPL‐Ofi (0.01–1%; treated group) or sterile saline (control group) for a period of 21 days. Ulcerated tissue was collected for analysis of histological parameters (inflammation score, number of polymorphonuclear, mononuclear, fibroblast/myofibroblasts and blood vessels), immunohistochemical (fibroblast growth factor 2 [FGF‐2]) and oxidative stress markers (myeloperoxidase [MPO] and glutathione [GSH]). After 21 days of treatment, body weight, net organ weight and plasma biochemical levels were measured. TPL‐Ofi, containing a total carbohydrate content of 65.5% and uronic acid at 2.8%, reduced oedema on the second day and increased the nociceptive threshold on the second and third days. TPL‐Ofi reduced mononuclear infiltrate on the second and MPO activity on the fifth day. TPL‐Ofi increased GSH levels on the second day, as well as fibroblast/myofibroblasts counts, neoangiogenesis and FGF‐2 levels on the fifth and seventh days. No changes were observed in body weight, net organ weight or toxicology assessment. Topical application of TPL‐Ofi exhibited anti‐inflammatory and antinociceptive effects, ultimately improving wound healing in cutaneous wounds.