<p>The data regarding the influence of active vitamin D supplementation on muscle mass and function in end-stage renal disease (ESRD) patients have been inconclusive. Our study aimed to determine the effectiveness of vitamin D supplementation on the alterations in muscle mass and function in peritoneal dialysis (PD) patients with sarcopenia. This single-center, randomized, open-label, parallel-controlled clinical trial was conducted at the Ningbo No.2 Hospital, which serves as a tertiary care center in the Ningbo region of Zhejiang Province, China. ESRD patients with sarcopenia and vitamin D insufficiency or deficiency (serum 25(OH)D levels &lt; 30 ng/mL) who were undergoing PD were recruited for the study. Participants were randomly allocated in a 1:1 ratio to either the intervention group (<i>n</i> = 25) or the control group (<i>n</i> = 25). Participants within the intervention group were prescribed alfacalcidol soft capsules at a daily dosage of 0.5&#xa0;µg. By contrast, participants assigned to the control group were explicitly prohibited from using alfacalcidol or any other pharmaceutical formulations that contained active vitamin D components. The primary endpoint was the improvement in skeletal muscle mass or function (a composite endpoint) from the baseline assessment to Week 48. Primary efficacy analyses were based on the intention-to-treat (ITT) population who completed randomization. Sensitivity analyses of the per-protocol (PP) population and the population adjusted for potential confounders were performed. Safety and tolerability were monitored. This trial was registered at the Chinese Clinical Trial Registry, ChiCTR2400084107. Participants had a good adherence to treatment. During the 48-week outpatient follow-up, 30.0% (15/50) of participants achieved improvement in muscle mass or function. Specifically, 48.0% (12/25) of participants in the alfacalcidol group and 12.0% (3/25) in the control group achieved improvement in muscle mass or function, yielding an absolute difference of 36.0% (95% CI 12.6% – 59.4%; <i>P</i> = 0.005), with a relative risk (RR) of 1.69 (95% CI 1.13–2.53). For the PP population, the results showed an absolute difference of 38.6% (95% CI 13.7% – 63.5%; <i>P</i> = 0.006), with a RR of 1.81 (95% CI 1.14–2.86), between the two groups. For the population adjusted for baseline age and serum 25(OH)D in the multivariate model, vitamin D supplementation was still significantly correlated with the improvement in muscle mass and function (odds ratio (OR) 11.89, 95% CI 1.92–73.5; <i>P</i> = 0.008). The incidence of adverse events did not differ between the two groups, and the daily administration of 0.5&#xa0;µg of alfacalcidol was well-tolerated. These results indicate that the administration of active vitamin D has the potential to improve muscle mass and function in ESRD patients with sarcopenia and vitamin D insufficiency or deficiency who were undergoing PD. Nevertheless, due to the risk of biases stemming from study limitations, these findings should be interpreted as exploratory, and the generalizability (external validity) of the results warrants further investigation.</p><p><b>Registration and Protocol Availability</b>: The trial has been registered with the Chinese Clinical Trial Registry (<a href="http://www.chictr.org.cn">http://www.chictr.org.cn</a>) under registration number ChiCTR2400084107, and the registration date is May 10, 2024. The detailed protocol can be accessed directly from the website.</p>