Topical antiseptics are widely used for superficial skin lesions. Although topical antiseptics are intended for external use, oral exposure has been reported. We report a fatal multiple-drug intoxication in an 87-year-old woman who had ingested eperisone, betahistine, other drugs, and a topical antiseptic containing naphazoline, chlorpheniramine, and dibucaine. Toxicological analysis by liquid chromatography-tandem mass spectrometry detected naphazoline, chlorpheniramine, and dibucaine in cardiac/peripheral blood at 0.40/0.07, 0.78/0.15, and 0.37/0.12 mg/L, respectively. Chlorpheniramine was at a toxicologically significant concentration, whereas the significance of naphazoline and dibucaine could not be assessed due to limited blood concentration data associated with toxicity. Eperisone was detected above the toxic range (11.1/0.10 mg/L), and betahistine was also detected (2.36/0.83 mg/L). All drugs detected in blood were detected in gastric contents, oral cavity fluid, and material collected around the mouth, while substantial amounts of eperisone, betahistine, and chlorpheniramine were detected in gastric contents. The cause of death was acute drug intoxication. This case highlights the challenges in interpreting postmortem findings involving topical preparations due to limited reference data and concurrent drug exposure. Detection of these compounds can provide circumstantial evidence of oral exposure and should be considered in forensic toxicological assessment.