Scleroderma (SD) is a rare and agnogenic autoimmune disease whose progression can be modified by medical or surgical intervention if detected early. Multimodality imaging makes early detection of SD possible based on the structural and functional findings from different imaging methods. Combining optical coherence tomography (OCT) with magnetic resonance angiography (MRA) and Doppler ultrasonography (DUS) to identify the typical structural and functional features that can exhibit significant differences between SD patients and healthy controls. In this study, six participants (three healthy volunteers and three SD patients) were recruited and clinically examined by a rheumatologist. Participants’ fingers were scanned by MRA, DUS, and OCT, respectively. MRA and DSU imaging results showed that SD patients exhibited thicker finger skin, a loss of blood vessels, and lower blood flow, whereas OCT captured the high-resolution morphology changes of the skin, epidermal, dermis, and subcutaneous layers, demonstrating a distinct loss of the dermo-epidermal junction in SD patients. Multimodal imaging techniques offer a more comprehensive characterization of the morphological and functional information of biological tissues, which can assist physicians to achieve a more accurate SD diagnosis.