Freshwater aquaculture plays a crucial role in addressing the growing demand for seafood, providing a sustainable solution, and contributing to global food security. It offers notable advantages for saltwater aquaculture in terms of cost-effectiveness, environmental management, and reduced ecological impact. As a system for farming aquatic organisms, aquaculture significantly contributes to human food production and addresses issues like protein shortages and diet-related diseases. However, it also faces challenges such as fish epidemics and ecosystem impacts. This Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-based systematic review focuses on the needs of both the modulation of chemical–physical environmental factors and natural ingredients used in feed formula to improve the wellness of farmed fish in freshwater aquaculture. We analyzed published articles between 1 January 2013 and 30 June 2024 using PubMed, Scopus, and Web of Science databases. The results highlighted the good effects of ultraviolet light (UV-C) treatment about bacterial infections and the use of oxolinic acid (OA) and alpha-lipoic acid (ALA) on fish welfare through diet. These factors highlighted the importance of dose-dependent applications of both environmental physico-chemical factors and natural feed ingredients. Tailoring diets with specific nutritional components is crucial to improve productive outcomes in freshwater aquaculture systems, ultimately supporting the health and welfare of farmed fish.