Systemic sclerosis (SSc) is a heterogeneous, chronic connective tissue disease, characterized by skin fibrosis as well as vascular and visceral lesions. It can involve the lungs, heart, kidneys, gastrointestinal tract, and bones. The orofacial manifestations of SSc can cause functional, aesthetic, and social distress, resulting in significant psychological implications for the patients. In recent decades, fat grafting improved the aesthetic outcomes in terms of volume deficiency, contour asymmetry, and skin elasticity of the face thanks to the regenerative action of the stem cells contained within it. We describe five cases of a patient with SSc treated with fat grafting used to correct volume loss and facial elasticity of the lips and perioral region on the middle and lower third of the face. All the patients received regular postoperative checks at weeks 1 and 2. A multiple choice questionnaire was administered to assess the degree of tolerability of the procedure. The reliability of the questionnaire was evaluated by calculating the Cronbach alpha using the MedCalc Statistical Software version 20.113. The aim of our study is to describe three different types of fat grafting used to correct volume loss and restore facial elasticity of the lips and perioral region on the middle and lower third of the face.