Natural extracts have been used as antimicrobial agents, and extracts of the rhizomes of the dragon’s blood plant (Jatropha dioica) and of the fruit of xoconostle ‘Ulapa’ (Opuntia oligacantha) are among these agents. To be able to use the extracts, it is necessary to eliminate their natural microbiota by the means of sterilization methods; however, the effects of thermal sterilization on their properties have not been evaluated. The objective of the study was to evaluate the physico-chemical, antioxidant, and antimicrobial properties of extracts of the rhizomes of dragon’s blood and the fruit of xoconostle, when not sterilized, and when sterilized by autoclaving. The contents of phenolic compounds, flavonoids, antioxidant, and antimicrobial activity against Streptococcus mutans were not affected in autoclave-sterilized extracts of dragon’s blood rhizomes, and naringenin, apigenin, galagina, vanillic, and caffeic acid were detected, while in autoclave-sterilized extracts of xoconostle fruits, the betalain content decreased, with galagin, gallic, vanillic, and p-coumaric acid being identified. The minimum inhibitory concentration for the extract sterilized by autoclaving dragon’s blood was 2 mg/mL, and for the extract sterilized by autoclaving xoconostle, it was 28 mg/mL. Both represent natural alternatives as antimicrobial agents against S. mutans.