<p>Regenerative therapeutic effect of bioactive fish by-products (gelatin and fish mucin) and botanical (shea butter) on wound healing of <i>Clarias gariepinus</i> was studied. Thirty-five fish of 312 ± 14&#xa0;g average weight were divided into seven groups, each comprising a fish and its four replicates: the gelatin group, mucin group, shea butter group, gelatin-shea butter homogenate group, mucin-shea butter homogenate group, positive control and negative control group Wound incision was made on each fish, then monitored for contraction rates, visual closure, and histological changes over 18&#xa0;days. Result obtained were subjected to appropriate statistical analysis using SPSS 16.0. It was observed that penicillin ointment produced the fastest and most complete healing (&gt; 60% closure), gelatin-based treatments (gelatin alone and gelatin + shea butter) closely matched penicillin’s performance, achieving near-comparable closure rates. Shea butter, mucin, and mucin–shea butter homogenate produced intermediate healing (50–55% closure) while the untreated group showed the slowest healing, underscoring the importance of active intervention. Histological analysis revealed penicillin-treated wounds with dense mononuclear infiltration, gelatin-treated wounds with moderate inflammation, shea butter-treated wounds with complete epidermal integrity, and mucin-treated wounds with minimal inflammation. The order of preference for the wound healing materials include: penicillin ointment<b> &gt; </b>gelatin &gt; gelatin-shea butter homogenate &gt; shea butter &gt; mucin-shea butter homogenate &gt; mucin. Among the natural wound-healing materials, gelatin consistently produced the most favorable results, closely matching the healing efficiency of penicillin ointment. Therefore, gelatin-based treatments should be prioritized to replace synthetic wound-healing materials in aquaculture, offering a sustainable, eco-friendly, and effective solution for fish health management.</p>