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Kalanchoe brasiliensis Cambess. is a native Brazilian plant popularly known as "saião", and the juice of its fresh leaves is traditionally used to treat several disorders, including inflammatory and infectious processes such as dysentery. The goals of this study were to characterize the phytochemical composition and investigate the antioxidant activity, the antibiotic effect, and the mode of action against Salmonella of the hydroethanolic extracts from K. brasiliensis leaves collected in the summer and spring Brazilian seasons. These extracts had their chemical composition established by high-performance liquid chromatography with diode-array detection. Total phenolic and flavonoid contents were spectrophotometrically determined. 2,2-Diphenyl-1-picryl-hydrazyl radical scavenging, phosphomolybdenum reducing power and β -carotene bleaching assays were carried out to evaluate the antioxidant capacity. Antibiotic potential was assessed by minimal inhibitory concentration against 8 bacterial ATCC® and 5 methicillin-resistant Staphylococcus aureus and 5 Salmonella clinical strains. The mode of action was investigated by time-kill, bacterial cell viability, and leakage of compounds absorbing at 280 nm assays against Salmonella . Chromatographic profile and UV spectrum analyses suggested the significant presence of flavonoid type patuletin and eupafolin derivatives, and no difference between both periods of collection was noted. Significant amounts of total phenolic and flavonoid contents and a promising antioxidant capacity were observed. Hydroethanolic extracts (70%, summer and spring) were the most active against the tested Gram-positive and Gram-negative bacterial strains, showing the bacteriostatic action of 5000 μ g/mL. Time-kill data demonstrated that these extracts were able to reduce the Salmonella growth rate. Cell number was reduced with release of the bacterial content. Together, these results suggest that K. brasiliensis is a natural source of antioxidant and antibacterial agents that can be applied in the research and development of new antibiotics for the treatment of Salmonella gastroenteritis because they are able to interfere in the Salmonella growth, probably due to cell membrane damage., Competing Interests: The authors declare that they have no conflict of interest regarding the publication of this research article., (Copyright © 2019 Oscar Alejandro Santos Mayorga et al.)