Background and objectives: Squill [Drimia maritima (L.) Stearn] is an important medicinal plant that has been used for medicinal purposes such as cardiovascular diseases and asthma since ancient times. Bufadienolides are the main compounds of this plant and are responsible for some reported adverse effects. In order to reduce adverse effects, different methods like boiling with vinegar were applied by traditional practitioners. In the present study, the acute oral toxicity, cytotoxic effects, proscillaridin A content and antibacterial properties of methanol and vinegar extracts of squill white variety were compared for exploring the efficacy of traditional processing method. Methods: Different doses of extracts (1000-5000 mg/kg) were administered during oral gavage in rats to analyze the acute oral toxicity. Cytotoxicity against HT-29, Caco-2 and NIH3T3 cell lines and antibacterial activity (Staphylococcus aureus, Staphylococcus epidermidis, Bacillus subtilis, Pseudomonas aeruginosa, Klebsiella pneumoniae and Escherichia coli) were investigated using MTT assay and conventional agar dilution method, respectively. Proscillaridin A content was evaluated in the extracts (vinager and methanol) by a validated high performance liquid chromatography method. Results: During the in vivo research no death or observed effect occurred in animals that received the extracts. Our results showed that all of the extracts exhibited no cytotoxic effects in experimented cell lines (IC50>1000 mu g/mL). Proscillaridin A was only detected in the methanol extract and no significant antibacterial effect was detected in methanol extract. Conclusion: According to results of the present study, processing squill with vinegar according to traditional experiences can reduce possible the side effects of bufadienolids.