Abstract Background Systemic sclerosis (SSc) is a rare connective tissue disease characterised by immune dysfunction, vasculopathy, cellular inflammation, fibrosis of the skin associated with multiple internal organs involvement. Ischaemic digital ulcers (IDU) of the hands commonly occur in patients with SSc adversely affecting functional independence. Purpose Aim of the study is to investigate the effectiveness of a rehabilitation protocol based on the combined use of ultrasound (US) therapy and therapeutic exercise in terms of ulcers healing, pain relief, and hand functioning in patients affected by SSc with IDUs. Moreover, we also investigated the safety of the proposed intervention. Study design Prospective before-after study. Methods We included 20 patients with IDUs secondary to SSc. All patients were treated with US combined with manual therapy, including McMennel joint manipulation, pompage mobilization technique and connective tissue massage, for 10 sessions. We evaluated softness, dyschromia, pain, and hand mobility using the Pressure Sore Status Tool (PSST), the Numerical Rating Scale (NRS), and the Duruoz Hand Index (DHI) at T0 and at the end of the treatment (T1). Results Treatment with US combined with manual therapy significantly reduced ulcers depth, improved ulcers margins, and reduced periwound skin damage (median PSST score 16 at T1, p<0.0001). Moreover, significant benefits were reported in terms of pain relief (NRS 3 at T1; p<0.0005), and hand function (DHI score 19 at T1; p<0.0005). Finally, this approach seems to be safe, without side effects reported at the end of treatment, along with an optimal compliance. Conclusion Therapeutic US combined with manual therapy should be used as additional intervention to manage IDUs in SSc patients.