Human AdipoRs and mPRs (members of the PAQR family) are seven-transmembrane receptors involved in regulating metabolism and cancer development, sharing structural similarities with G protein-coupled receptors (GPCRs). The plant PAQR-like sensors (PLS) are homologous to human PAQR, but their molecular functions are still unclear. Here, we found that PLSs associate with cell surface receptor-like kinases (RLKs) through KIN7 and positively regulate plant immune responses, stomatal defense, and disease resistance. Moreover, PLSs activate heterotrimeric G-proteins (Gαβγ) to transmit immune signaling and partially regulate the exchange of GDP for GTP on GPA1. We further revealed that the immune function of PLSs is conserved in rice and soybean, contributing to resistance against multiple diseases. Notably, heterologous expression of human AdipoRs in Arabidopsis can mimic the immune functions of PLSs. Collectively, our findings demonstrate that PLS is a key modulator of plant immunity through G-protein pathway, and highlight the potential application of human genes in enhancing plant disease resistance.