Background Protein-energy wasting (PEW) is common in patients undergoing hemodialysis (HD). Studies have assessed the positive effect of oral nutritional supplementation (ONS) or resistance exercise (RE) on nutritional status (NS) markers in patients undergoing HD. Methods The aim of this study was to assess the effect of ONS and RE on NS and the quality of life (QOL) of 36 patients undergoing HD. In a randomized clinical trial, patients were divided into the following two groups: a control group (ONS) that received a can of ONS during their HD sessions and an intervention group (ONS + RE) that received a can of ONS and underwent a 40-min session of RE during their HD sessions. Both interventions lasted 12 weeks. The patients' anthropometric, biochemical, dietetic and bioelectrical impedance measurements as well as their QOL, evaluated using the Kidney Disease Quality of Life Short Form, were recorded. Results At baseline, 55.5% of patients presented with PEW according to International Society of Renal Nutrition and Metabolism criteria (20 patients). We found statistically significant changes from baseline in both groups, such as increases in body weight, body mass index, midarm circumference, midarm muscle circumference, triceps skinfold thickness, fat mass percentage, handgrip strength, phase angle and serum albumin. A decrease in the prevalence of PEW was observed in both groups at the end of the intervention. A delta comparison between groups showed no statistically significant differences in the anthropometric and biochemical parameters. No significant improvement was observed in QOL and body composition measured by bioimpedance vector analysis. Dietary energy and protein intake increased significantly during the study period for all patients. Conclusion Oral nutritional supplementation during HD improves NS. The addition of RE during HD does not seem to augment the acute anabolic effects of intradialytic ONS on NS.