Systemic sclerosis (SSc) is characterized by microvascular damage and fibrosis of the skin and internal organs. Non-healing skin ulcers, mainly non-venous leg ulcers, represent one of the most challenging complications. Platelet gel (PG) is a hemocomponent containing numerous growth factors, potentially useful for tissue reparation. This pilot open study aimed to evaluate the effect of PG in 12 SSc patients with skin ulcers resistant to conventional therapies from at least 6 months. PG was applied in the wound bed twice weekly for 2 weeks, then once a week for 12 weeks; in all cases, the ongoing treatments remained unchanged at the time of PG applications. Skin ulcers were evaluated at 0, 12 and 24 weeks; the patient's quality of life was also evaluated using the visual analogical scale (VAS) and the health assessment questionnaire (HAQ). During the 6-month follow-up, the skin ulcers consistently improved in 10/12 patients, with complete healing in 4. At the last evaluation, wound size reduced from 23.4 ± 14.9 SD to 2.3 ± 2.2 SD cm(2) (p < 0.0001). Patient's quality of life markedly improved: VAS decreased from 87.08 ± 13.5 to 57.9 ± 12.6; p < 0.0001 and HAQ from 0.73 ± 0.43 to 0.57 ± 0.22; p < 0.0001. PG may represent a novel therapeutic option for SSc skin ulcers refractory to conventional treatments.