Suicidal behaviors constitute a major global public health problem, with sexual minority groups showing a higher risk of engaging in such behaviors. This study aimed to analyze the influence of hopelessness, life satisfaction, and spirituality on suicide risk according to self-reported sexual orientation. A total of 532 individuals participated (M = 31.15 years, SD = 12.002). Of these, 39.8% identified as heterosexual, 34.2% as gay or lesbian individuals, and 25.9% as bisexual. Participants were assessed using the Plutchik Suicide Risk Scale, Beck’s Hopelessness Scale, the Beliefs and Values Scale, and Diener’s Satisfaction with Life Scale. The results indicate that 52.9% of bisexual participants and 41.2% of gay and lesbian participants presented a high suicide risk, compared with 15.6% of heterosexual participants. Individuals with a high suicide risk reported higher levels of hopelessness (p < 0.001), lower levels of life satisfaction (p < 0.001), and similar levels of spirituality. The proportion of variance explained in suicide risk was 42.8% among bisexual participants, 34.2% among gay and lesbian participants, and 29.9% among heterosexual participants. Hopelessness predicted a similar proportion of across groups (β = 0.446 in heterosexuals, β = 0.447 in gays and lesbians, and β = 0.457 in bisexuals). Life satisfaction showed a protective predictive effect, with β = −0.241 in bisexual participants, followed by gay and lesbian participants (β = −0.186) and heterosexual participants (β = −0.137). Spirituality was significant only among gay and lesbian participants (β = 0.133) and bisexual participants (β = 0.214). Sexual minority groups exhibited a higher risk of suicide, with life satisfaction—but not spirituality—acting as a protective factor.