(1) Background: Perilla frutescens (L.) Britt. is an important pharmaceutical crop that remains a focus point for researchers worldwide due to its complex phytochemical constituents, medicinal effects, and nutraceutical properties. The literature data are based on animal and cell culture studies, so the clinical evidence for the therapeutic effects is poorly outlined. The aim of this review was to provide an updated and thorough understanding of Perilla frutescens applications in clinical practice using data derived from human studies, and to outline the potential directions and perspectives for further studies on this crop. (2) Methods: Medline, Embase, and Cochrane databases were used to find relevant studies. All interventional studies that evaluated the effect of Perilla frutescens in human subjects were assessed. (3) Results: The main perspectives that can be contoured from the presented literature evaluation are an important clinical effect of Perilla frutescens extracts on allergic rhinoconjuctivitis, especially in young populations, a potent hypolipemiant effect that, in conjunction with increased serum biological antioxidant potential, determines significant improvements in cognitive function and a wide variety of miscellaneous clinical effects that need further exploration. (4) Conclusions: Supplementary research is needed in order to demonstrate the therapeutic effects of Perilla frutescens in controlled clinical settings.