Perilla frutescens leaves are often used in East Asian gourmet food. In this study, we investigated the hepatoprotective effects of P. frutescens leaves grown in different concentrations of sucrose (0, 115, 175 and 235 mM sucrose) leading to four samples of perilla leaf extracts (PLEs). Based on caffeic acid level and antioxidant activities, further experiments were conducted using perilla leaf extracts treated with 6% sucrose compared with non-treated perilla leaf extracts as a control. Oral intubation with non-treated perilla leaf extracts or perilla leaf extracts treated with 6% sucrose (1000 mg/kg b.w. rat) for 5 days was conducted before treatment with a single dose of tert-butyl hydroperoxide (0.5 mmol/kg b.w., i.p.) led to a significant reduction of hepatic toxicity in the perilla leaf extracts treated with 6% sucrose. We demonstrated that P. frutescens with higher contents of caffeic acid was produced, and that sucrose could play a role in the induction of this secondary metabolite. Sucrose-treated perilla leaves, which had better antioxidant activities than untreated leaves, can be used as a potential dietary source.