As a receptor for transforming growth factor-β, nodal and activin, activin receptor-like kinase 7 (ALK7) previously acts as a suppressor of tumorigenesis and metastasis, which has emerged to play a key role in cardiovascular diseases. However, the potential effect and molecular mechanism of ALK7 on vascular smooth muscle cells' (VSMCs) phenotypic modulation have not been investigated. Using cultured mouse VSMCs with platelet-derived growth factor-BB administration, we observed that ALK7 showed a significantly increased expression in VSMCs accompanied by decreased VSMCs differentiation marker genes. Loss-of-function study demonstrated that ALK7 knockdown inhibited platelet-derived growth factor-BB-induced VSMCs phenotypic modulation characterized by increased VSMCs differentiation markers, reduced proliferation, and migration of VSMCs. Such above effects were reversed by ALK7 overexpression. Notably, we noticed that ALK7 silencing dramatically enhanced PPARγ expression, which was required for the attenuated effect of ALK7 knockdown on VSMCs phenotypic modulation. Collected, we identified that ALK7 acted as a novel and positive regulator for VSMCs phenotypic modulation partially through inactivation of PPARγ, which suggested that neutralization of ALK7 might act as a promising therapeutic strategy of intimal hyperplasia.