<p>Renal risk variants in the apolipoprotein L1 (<i>APOL1</i>) gene confer protection against trypanosomiasis, but these risk variants (G1 and G2 variants) also predispose to kidney disease among individuals, especially from Sub-SaharanAfrica. Currently, the mechanisms of how these renal risk variants induce kidney damage are not precisely defined, but lysosomal and mitochondrial dysfunction, altered ion channel activity, altered autophagy, and disordered immunity are suggested. Currently, there is no specific treatment for <i>APOL1</i> kidney disease (<i>APOL1</i>-KD) although several potential disease-specific therapeutic agents are being evaluated in clinical trials. Non-specific interventions include proteinuria screening, salt restriction, and renin-angiotensin-aldosterone system inhibition but are not sufficient to prevent kidney disease progression in <i>APOL1</i>-KD. Given the lack of specific treatment options, more efforts are necessary to reduce kidney disease progression. Sodium glucose co-transport-2 (SGLT2) inhibitors (SGLT2i) are gaining attention for benefits in proteinuric kidney diseases and exert many beneficial effects which theoretically may be beneficial in the context of <i>APOL1</i>-KD. These beneficial effects include but are not limited to increased natriuresis, decreased proteinuria/albuminuria, and mitochondrial dysfunction. SGLT2i have antioxidant, anti-inflammatory and anti-fibrotic effects. In the current review, we highlight the potential reasons for exploring the use of SGLT2i in <i>APOL1-</i>KD. Future studies are warranted to explore if SGLT2i use can provide protection in <i>APOL1</i>-KD</p>