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Chronic Kidney Disease is a global health challenge and its early diagnosis is still a challenge, particularly when relying on conventional biomarkers like serum creatinine. In this systematic review, PRISMA guidelines were followed with a comprehensive search on various databases focusing on studies assessing estimated cystatin C levels, and creatinine levels among patients with chronic kidney disease, type 2 diabetes mellitus and hypertension. The Joanna Briggs Institute's critical assessment tool was used to estimate quality and risk bias of included studies. This systematic review included 21 studies with maximum studies demonstrating cystatin C based eGFR may provide more reliable and accurate estimate of kidney function than creatinine based eGFR, specifically for early identification of kidney dysfunction. The findings suggest that serum cystatin C is an early diagnostic and prognostic marker and its incorporation into routine testing will increase the clinical utility by improving risk stratification. In general, this systematic review highlights the diagnostic and prognostic utility of serum cystatin C for early detection of kidney dysfunction.