Background and Aim: Wound healing is a complex process comprised of several distinct phases. An imbalance in any of the stages creates a chronic wound with the potential to cause life-threatening complications for patients. Chitosan (CS) is a biopolymer that has shown to positively impact the different healing phases. This systematic review aimed to evaluate the anti-inflammatory and immunomodulatory properties of CS-based wound therapy for the skin healing process after an injury. Methods: A systematic review was conducted in November 2021 following the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. The PubMed, Embase, Google Scholar, and Cochrane online databases were queried to capture all publications in the past 10 years that investigated the CS effects on inflammation and immune reaction. Results: A total of 234 studies were screened after removing duplicates and 14 articles fulfilled our inclusion and exclusion criteria. In the studies, CS was combined with a wide range of products. One clinical trial was found that treated patients with diabetic foot ulcers. All animal models in the studies used a full-thickness skin wound to test the effectiveness of CS in the healing process. Decreased proinflammatory cytokine levels, a shortened inflammatory phase and accelerated wound closure was observed in all of the studies. Conclusions: CS proved to be a feasible, versatile, and multifaceted biomaterial that enhances the biological response to a skin injury. When combined with other products, its potential to boost the healing process through regulation of the inflammatory and cellular activity is increased. Relevance for Patients: Although few clinical trials have been completed, CS has become an excellent alternative to modulate the local inflammatory response promoting wound healing. Especially in patients with associated comorbidities that affect the typical resolution of skin healing, such as diabetes and vascular insufficiency. Therefore, using bioactive wound dressings based on CS combined with nanoparticles, growth factors, lived cells, or medications released in a controlled manner positively impacts patient life by shorting the wound healing process.