Different solvent extracts of Pereskia bleo leaves were evaluated for total phenolic content (TPC) and antioxidant activities based on the Folin–Ciocalteu test and DPPH scavenging activities. The antibacterial activities against four bacteria, namely, Gram-positive bacteria: Streptococcus pyogenes ATCC 19615 (SP) and Staphylococcus aureus ATCC 29737 (SA) and Gram-negative bacteria: Escherichia coli ATCC 10536 (EC) and Pseudomonas aeruginosa ATCC 9027 (PA), were also performed based on the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) assays. The findings demonstrated that both the methanolic and chloroform extracts displayed strong activities against SA, SP, EC, and PA while the hexane extract demonstrated the weakest activities towards all the four bacteria. The methanolic extract also exhibited higher TPC and possessed higher antioxidant activity with the IC50 value 33.83 µg/mL compared to the chloroform and hexane extracts. As such, the methanolic extract has a higher ability to scavenge free radical compared to other extracts. Due to the interesting result, activities are shown by the methanolic and chloroform crude extracts of P. bleo; hence, the study has been extended to the isolation of bioactive compounds to uncover its great potential as a natural source for antibacterial and antioxidant agents.