Pharmaceutical products that mix natural raw materials are subject to unavoidable contamination with microorganisms from the environment and animals. This study focused on the effect of radiation on the quality of primary packaged pills, which are crude drug products. The pills, which were sealed in a sack for primary packaging laminated with polyethylene terephthalate, polyethylene, and aluminum foil, were irradiated by gamma rays or electron beam (EB). The survival counts of bacteria were reduced to 103 CFU/g or less by 6 kGy of irradiation. The counts of the spore-forming bacteria Bacillus megaterium, B. cereus, and Brevibacillus brevis in the pills were reduced to not over 100 CFU/g after 10 kGy irradiation. Although some of the cinnamaldehyde in the pills was oxidized to cinnamic acid, the decomposition of swertiamarin, berberine, glycyrrhizin, and cinnamaldehyde in the pills after 10 kGy irradiation were within the analytical accuracy by high-performance liquid chromatography. Gamma-ray or EB treatment at the final production of crude drug preparations was within the permissible standard value for the non-aqueous preparations for oral administration, with no statistically significant change in the indicator ingredients of crude drugs.