Protein-energy wasting (PEW) affects about 50-75% of patients with chronic kidney disease (CKD), particularly those who are on maintenance hemodialysis (MHD). This study evaluated the efficacy and tolerability of an oral nutritional supplement in Indian patients receiving MHD. This was a 3-month, prospective, open-label, and single-centered study. Eligible participants supplemented their regular diet with one sachet (40 gm) of oral nutritional supplement powder twice daily for 90 days. The study efficacy endpoints were mean change in acute phase proteins (albumin and prealbumin), anthropometric measurements [weight, body mass index (BMI), and triceps skin fold thickness], handgrip strength, hemoglobin, total iron binding capacity (TIBC), potassium, and phosphorus levels, malnutrition score (MS)-modified subjective global assessment (modified SGA), malnutrition inflammation score (MIS), and nutritional status. The study population comprised 36 (42.9%) men and 48 (57.1%) women with a mean age of 54.85 ± 15.50 years. A paired sample t-test was used to compare the baseline with end-of-study values for continuous variables. Serum albumin, prealbumin, hemoglobin, and phosphorus levels remained stable throughout the study period. The mean change in weight, BMI, triceps skin fold thickness, handgrip strength, and TIBC for the overall study population was 1.11 kg (1.82%, p < 0.0001), 0.46 kg/m2 (1.98%, p < 0.0001), 3.47 mm (30.78%, p < 0.0001), 6.05 kg (44.98%, p < 0.0001) and 11.80 µg/dL (6.06%, p < 0.0001), respectively. At the end of the study period, there was a significant (p < 0.0001) improvement in the SGA and MIS scores. Further, there was a significant improvement in nutritional status as demonstrated by the overall intake of calories (p < 0.001), proteins (p < 0.0001), carbohydrates (p = 0.003, and fats (p < 0.0001). Protein-energy malnutrition is a strong predictor of morbidity, mortality, and poor outcomes in CKD patients. A scientifically designed formula in accordance with KDOQI standards was able to improve the nutritional status, overall body composition, sarcopenia, and quality of life in CKD patients on MHD.