Systemic sclerosis (SSc) is a complex connective tissue disorder characterized by fibrosis, vascular dysfunction, and immune dysregulation. This chapter explores investigational therapies for SSc-related bowel disease, focusing on emerging pharmacologic agents targeting motility disorders. Current therapeutic strategies focus on symptom management and disease modification through several agents. Despite advancements, challenges remain in predicting disease progression and optimizing individualized treatment approaches. While emerging targeted therapies show promise, further clinical trials are essential to evaluate their long-term efficacy, safety, and impact on disease progression.