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<i>Penicillium expansum</i> is the predominant causal agent causing blue mold in postharvest fresh <i>Codonopsis pilosula</i> during storage. The pathogen reduces the yield and affects the quality of <i>C. pilosula</i> and even generates patulin, threatening human health. In this study, postharvest fresh, healthy <i>C. pilosula</i> was sprayed with <i>P. expansum</i>, and the control effect of ozone on postharvest diseases of <i>C. pilosula</i> was studied, and the effect of ozone on the contents in the main active ingredients of <i>C. pilosula</i> was compared; finally, the effect of ozone on reactive oxygen species (ROS) metabolism in <i>C. pilosula</i> was analyzed. The results showed that 2 mg L⁻¹ ozone application significantly inhibited the occurrence of postharvest blue mold caused by <i>P. expansum</i>, reduced weight loss rate, controlled the accumulation of patulin and maintained the contents of the main active components in <i>C. pilosula</i>. The study will provide a theoretical basis for ozone treatment to control the occurrence of postharvest diseases of <i>C. pilosula.</i>