Perilla (Perilla frutescens, PF) is an annual labiaceae herb that can be used as vegetable, seasoner, and herb, which mainly includes red PF (P. frutescens var. crispa) and green PF (P. frutescens var. frutescens). Red and green Perilla is mainly used for medicine and food, respectively. In order to explore the differences between these two Perilla cultivars and the effects of origin on them, we studied the components of 130 Perilla samples from different origins by ultra-high performance liquid chromatography quadrupole-time-of-flight mass spectrometry combined with partial least squares discriminant analysis and orthogonal partial least squares discriminant analysis. In this study, 57 potential compounds were analyzed, mainly including organic acids, flavonoids, terpenoids, and anthocyanins. In different varieties of Perilla, anthocyanins were found only in red PF. In addition, the content of four flavonoids, two organic acids, and one coumarin in red PF is much higher than that in green PF. Among the same variety of Perilla, the contents of three metabolites were higher in the north of China for red Perilla, while five metabolites were higher in the south of China for green Perilla. Overall, this research provided a basis for distinguishing different varieties and sources of Perilla through the differential metabolites of Perilla.