Wnt signaling plays a key role in embryonic patterning and morphogenetic movements. The secreted Frizzled-related proteins (sFRPs) antagonize Wnt signaling, but their roles in development are poorly understood. To determine whether function of sFRPs is conserved between amphioxus and vertebrates, we characterized sFRP2-like function in the amphioxus, Branchiostoma belcheri tsingtauense (B. belcheri). As in other species of Branchiostome, in B. belcheri, expression of sFRP2-like is restricted to the mesendoderm during gastrulation and to the anterior mesoderm and endoderm during neurulation. Functional analyses in frog (Xenopus laevis) indicate that amphioxus sFRP2-like potently inhibits both canonical and non-canonical Wnts. Thus, sFRP-2 probably functions in amphioxus embryos to inhibit Wnt signaling anteriorly. Moreover, dorsal overexpression of amphioxus sFRP2-like in Xenopus embryos, like inhibition of Wnt11, blocks gastrulation movements. This implies that sFRP2-like may also modulate Wnt signaling during gastrulation movements in amphioxus.