BackgroundDespite the prevalence of sexual distress and dysfunction in older adults in general and stroke and colorectal cancer survivors in particular, access to specialized care is limited by organizational barriers and stigma, embarrassment, and discrimination. The internet allows reaching services that would otherwise be difficult or impossible to reach, and as smartphones are personal (intimate) technologies, they are a promising vehicle to close this gap. However, research focusing on smartphone-delivered sexual health promotion programs is scarce.ObjectiveThis study aims to assess the acceptability, feasibility, and preliminary efficacy of Anathema, an 8-week, iOS/Android smartphone–delivered, individually tailored, cognitive-behavioral sexual health promotion program developed to improve relationship and sexual satisfaction, sexual functioning, sexual distress, sexual pleasure, and health-related quality of life (HRQoL) in older adults, colorectal cancer survivors, and stroke survivors compared to treatment as usual in a waiting-list control condition.MethodsTwo-arm, parallel, open-label, waiting list, feasibility, pilot randomized controlled trials (RCTs) will be conducted involving older adults, stroke survivors, and colorectal cancer survivors. The primary outcomes are the acceptability, usability, and feasibility of Anathema. Sexual function, relationship and sexual satisfaction, sexual pleasure, sexual distress, anxiety, depression, and HRQoL are the secondary outcomes. This study has been reviewed and approved by the ethics committees of Instituto Português de Oncologia do Porto Francisco Gentil, Europacolon Portugal, Faculty of Psychology and Educational Sciences, University of Porto, and Sigmund Freud University (approval numbers: CES218R/021, CES19/023, and 2022/01-05b).ResultsThis project is funded by the European Commission through the Active and Assisted Living (AAL) Programme (reference: AAL-2020-7-133-CP) from April 2021 to December 2023. Recruitment for the pilot RCTs started on January 2023 in Portugal, Austria, and the Netherlands and is currently ongoing. As of May 2023, we randomized 49 participants in the trials. We expect to complete the RCTs in September 2023. The results on the acceptability, feasibility, and preliminary efficacy of Anathema are expected in the second semester of 2023. We expect Anathema to be highly accepted by the populations under study; to prove feasible to scale up to parent RCTs; and to be potentially efficacious in improving sexual functioning, relationship and sexual satisfaction, sexual distress, sexual pleasure, and HRQoL in older adults, colorectal cancer survivors, and stroke survivors compared to treatment as usual in a waiting-list control condition. The study results will be published in open-access venues according to COREQ (Consolidated Criteria for Reporting Qualitative Research) and CONSORT EHEALTH (Consolidated Standards of Reporting Trials of Electronic and Mobile Health Applications and Online Telehealth) guidelines.ConclusionsThe study results will inform the refinement and scale-up of Anathema. Anathema’s wider-scale implementation can potentially promote the sexual health of largely neglected user groups such as older adults, colorectal cancer survivors, and stroke survivors.International Registered Report Identifier (IRRID)DERR1-10.2196/46734