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A wide variety of plants in the Philippines are used to address several medical ailments; however, many of which have not yet undergone thorough pharmacological studies. The problem on the possible side effects caused by these medicinal preparations has, therefore, increased the interest in validating their safety for human use. The present study was conducted to determine the cytotoxicity of five common local medicinal plants. Annona muricata L., Cymbopogon citratus DC., Graptophyllum pictum (L.) Griff, Jatropha curcas L., and Piper betle L. were selected and subjected to crude aqueous leaf extraction. Extracts were then investigated for cytotoxicity potential using brine shrimp lethality assay. The experiment resulted in median lethal time (LT50) values ranging between 21.23 to 24.06 hours. In addition, all these extracts had median lethal concentrations (LC50) lower than 1.00 mg/mL, suggesting the presence of cytotoxic constituents that could further be investigated both for safety and for anticancer potential.