Agri-food by-products are abundant in sub-Saharan Africa (SSA) yet are frequently discarded or downgraded to low-value uses despite being concentrated sources of functional fractions, including polyphenols (flavonoids, phenolic acids), carotenoids/pigments, dietary fiber and pectins, proteins/peptides, oils, and enzymes (e.g., bromelain). This review aimed to synthesize evidence on how climate-smart utilization of smallholder-generated residues can advance African food systems while addressing gender equity, which mediates who controls by-products, adopts technologies, and captures returns. Using a narrative review design, peer-reviewed articles and authoritative institutional reports or institutional provenance were compiled from major scholarly databases and institutional repositories. The synthesis indicates that common SSA residues—cereal brans/husks, cassava peels, fruit peels/kernels, oilseed cakes, and brewery spent grains—often contain higher bioactive concentrations than edible fractions and can be upgraded via low-cost, decentralized pathways such as drying, milling, fermentation/biotransformation, detoxification, and simplified “green” extractions (ethanol/water, ultrasound-assisted extraction, microwave-assisted extraction), alongside basic stabilization steps and food-safety practices. A conceptual framework links contextual driver (climate variability, seasonality, norms, tenure, markets, policy) to gender-differentiated resource access, shaping CSA outcomes across adaptation (income diversification), mitigation (waste reduction), and productivity/value addition. Case evidence from Nigeria (cassava peel flour and fermentation to reduce cyanogenic glycosides), Ghana (mango peel powders/extracts and potential cooperative pectin supply), and Kenya/East Africa (brewer’s spent grain and sorghum bran fortification) shows women lead post-harvest processing yet face credit, time poverty, equipment, extension, quality-certification, and market barriers, with gender-blind formalization risking elite capture. Gender-responsive technology design, inclusive/blended finance, cooperatives, tailored extension, and risk-based food-safety governance are therefore critical to enable safe market entry, equitable benefit sharing, and scalable climate-smart valorization in SSA.