Background: Polydrug use in the context of chemsex is commonplace among gay, bisexual, and other men-who-have-sex-with-men (GBMSM). This study aimed to examine differences among GBMSM who engaged in chemsex without using methamphetamine (M-), used methamphetamine but not gamma-hydroxybutyric acid/gamma-butyrolactone (GHB/GBL) (M+G-), and who used both drugs (M+G+). Specifically, we compared differences in mental health experiences, as well as physical, social, and psychological harms associated with chemsex. Methods: Adult GBMSM participants with experience of chemsex in the past 12 months participated in a cross-sectional online survey in Taiwan and self-reported their sociodemographic background, sexual behavior, mental health, and harm experiences following a chemsex session. We used univariable and multivariable logistic regression to assess the different experiences of harm and mental ill-health among GBMSM in the M-, M+G-, and M+G+ groups. Results: Out of 510 participants who completed all items included in the analysis, 24.1% were classified as M-, 36.9% as M+G-, and 39.0% as M+G+. Nearly 85% of men in the M+G+ group reported at least one social harm after a chemsex session, followed by M+G- (69.7%) and M- (37.4%). Both physical and psychological harms presented similar gradient proportions among M+G+, M+G-, and M-. In relation to mental health, multivariable logistic regression indicates those in the M+G+ group were significantly more likely to report suicide ideation compared to those in M- (OR = 2.40, 95% CI = 1.28 to 4.50). Conclusion: GBMSM who used both methamphetamine and GHB/GBL in a chemsex context were more likely to report experience of harms and suicide ideation than those who used a single drug or engaged in chemsex without methamphetamine or GHB/GBL. Harm reduction should not only focus on the prevention of HIV and STIs but seek to minimize psychosocial harms for GBMSM, which appear to have differential impact according to different drug use.