Antimicrobial activity from red dragon fruit peel extract was observed in this study. The aim of this research was to determine antimicrobial activity of red dragon fruit peel extract in inhibiting pathogenic microorganisms, specifically their cell damages. The best maceration was carried out using combination of ethanol:ethyl acetate (80:20) for six hours at 26°C. The result showed that 10% extract could inhibit the growth of Pseudomonas sp., E. coli, S. aureus, and B. cereus (6.83-8.33 mm) but could not inhibit Penicillium sp. and Mucor sp. The most sensitive bacteria was B. cereus based on MIC and MBC values (0.60% and 2.40%). The extract was also effective to inhibit spores of B. cereus (9.08 mm), protoplast and spheroplast condition (10.55-13.05 mm). The 10% extract had similiarity to streptomycin 50 ppm and penicillin G 10 ppm for S.aureus and B.cereus and streptomycin 10 ppm and penicillin G 100 ppm for E. coli and Pseudomonas sp. The calcium and potassium leakage of bacteria were detected by AAS and morphology cell damages which were analyzed by SEM. Furthermore, PEG could not purify the betalain pigment of the extract.