Capsicum genus contains many species of sweet and hot chili peppers. Capsicum frutescens is one of the important chili peppers that used as flavor, aroma and spices in the national cuisine. It has also been used as medicinal agents. The phytochemical compound which is responsible for the pungency is capsaicin. For control safety consumption, therefore the toxicity or side effect needs to be investigated. The aim of this research evaluated the amount of total phenols contents from different factors such as colors (red and green) and fruit parts (pericarp, capsaicin gland or placenta, and seed) of C. frutescens aqueous extraction in 1, 3, 5, 10 and 24 hours. The highest total phenolic content was shown in the 24 h extraction. So, this extraction time was used to investigate the cytotoxicity and histopathological alteration by using brine shrimp, Artemia salina as an animal model. Ten adults A. salina were incubated at room temperature for 24 h with various concentrations of chili. The mortality number of A. salina was recorded and the median lethal concentration value was calculated. The highest toxicity was reported in the green pericarp group. The primarily target organ was the intestine of brine shrimp. Enterocytes showed abnormal morphology such as edema, hyperplasia, disorganized arrangement, and finally necrosis. Moreover, the pericarp of the green chili showed the most severe results. It can be concluded that different colors and fruit parts of C. frutescens show different amounts of phenolic content and correlate with cytotoxicity leading to the severity of histopathological alteration in A. salina.