Loneliness is an enduring global health issue. Effective evidence-based loneliness interventions exist but lack sufficient scale to reach many who might benefit from them. Single-session interventions (SSIs), which aim to condense the core elements of evidence-based treatments into brief and broadly acceptable self-guided experiences, offer an opportunity to make robust guidance for overcoming loneliness much more accessible. This dissertation’s objective was to inform the development of effective and broadly-appealing SSIs for loneliness. Study 1 (n = 908) showed that neither a 20-minute SSI version (p = 0.22) nor a 1-hour 3-session version of a self-guided online loneliness intervention (p = 0.23) changed loneliness over four weeks more than an active control SSI did. However, participants reported finding both loneliness interventions more appealing and valuable than the control (ps < 0.02). While some participants reported that the loneliness interventions had a lasting positive impact, the interventions did not appear to be more useful on average than an active control among lonely people aged 16 and older with internet access. Study 2 explored if popular online content was more effective at reducing distress than typical researcher-created SSI content among a sample of mostly crowdworkers struggling with psychological distress. The study (n = 916) showed that a popular online content-centered mental health SSI did not affect participants’ distress over four weeks differently than a mental health SSI with researcher-created content (p = 0.09) or finding content independently on the web (p = 0.42). On the contrary, participants assigned to the researcher-created SSI reported greater improvement than those assigned to the popular online content-based SSI in depressive symptoms (b = -0.44, p = 0.03) and loneliness (b = 0.29, p = 0.04), on average. Future work should aim to improve SSIs’ effectiveness, identify populations for which SSIs are most effective, and implement SSIs in accessible and appealing ways.