Objectives: Post-stroke fatigue (PSF) is an experience characterized by an early feeling of exhaustion with fatigue, a lack of energy, and difficulty in exertion, both motor and cognitive. To counteract fatigue and limit its effects on activities of daily living, the use of vitamins and minerals is known in addition to the pharmacological approach. However, few studies have evaluated the effect of vitamin and mineral supplementation on fatigue management. SiderAL® Med is a food for special medical purposes with a complete formulation containing vitamins, sucrosomal minerals, copper and algal calcium. The aim of the study is to evaluate whether nutritional supplementation with SiderAL® Med improves the symptom of fatigue and motor and cognitive function in stroke patients. Design: This is a pilot, randomized study with a control group. Setting: Post-Acute Rehabilitation Unit of the Fondazione Policlinico “A. Gemelli” IRCCS. Participants: Twenty-four patients with stroke outcomes, admitted to rehabilitation, were recruited and randomized into the experimental group (Sid-G) and the control group (CG). Intervention: The Sid-G patients, in association with the pharmacological and rehabilitation therapy foreseen during hospitalization, took SiderAL® Med, one sachet per day for 8 weeks, while the CG patients underwent only the pharmacological and rehabilitation therapy foreseen in the daily routine. Measurements: All patients were assessed at baseline (T0), after 4 weeks (T1), after 8 weeks (T2) and after 12 weeks (T3) for motor and cognitive fatigue, balance, walking, functional capacity, cognitive performance, autonomy, quality of life and body composition. Results: Both Sid-G and CG patients showed significant improvement on most rating scales between T0-T1-T2-T3 (p = 0.0001). When comparing the two groups, a statistically significant difference emerged in favor of Sid-G with regard to motor fatigue (p = 0.007), cognitive fatigue (p = 0.009) and total fatigue (p = 0.034); balance (p < 0.001), functional capacity (p < 0.001); cognitive performance (p = 0.004); bone mineral content (p = 0.005), lean mass (p = 0.005), total mass (p < 0.001) and percentage of fat mass (p = 0.039). Conclusion: Nutritional supplementation with SiderAL® Med, in concert with intensive rehabilitation treatment, appears to be effective in managing fatigue and improving motor and cognitive performance and body composition, representing a valuable tool to associate with rehabilitation treatment in stroke patients.