Background: University students with depression and anxiety do not easily receive or seek treatment; therefore, internet-based interventions have been suggested to be a promising way to improve treatment accessibility and availability. However, it has not been examined whether a guided, culturally adapted, transdiagnostic, internet-based intervention is effective for treating symptoms of depression, anxiety, or both among university students in Indonesia. Objective: This study aims to investigate the feasibility (acceptability and satisfaction, usability, and uptake) of a guided, culturally adapted, transdiagnostic, internet-based intervention among university students with symptoms of depression, anxiety, or both in Indonesia. Methods: Students from Universitas Gadjah Mada, Yogyakarta, Indonesia, were screened for symptoms of depression, anxiety, or both, and filled online informed consent, demographic questionnaires, and a quality of life measure at pretreatment assessment (T0). Subsequently, the participants started the intervention. Seven weeks after T0, the primary outcomes of this feasibility study were analyzed at posttreatment assessment (T1) using the 8-item Client Satisfaction Questionnaire (CSQ-8) and the System Usability Scale (SUS). Mean and SDs for the CSQ-8 and SUS were calculated to examine feasibility. Within-group secondary outcomes (depression, anxiety, and quality of life) were inspected for outliers and normal distribution. Paired-sample t tests were used to investigate differences between time points of secondary outcomes. A mixed-method approach of quantitative and qualitative analyses was adopted. Both the primary and secondary outcomes were additionally explored with an individual semistructured interview and synthesized descriptively. Results: A total of 50 participants completed the intervention. We found a moderate to high level of satisfaction and acceptability, a slightly below-average level of desirable usability (≥70), and an adherence rate of 52% which was higher than expected given the novelty of the intervention. Results for the secondary outcomes indicated a decrease in depression and anxiety. For depression, the overall mean difference between the 2 time points for depression was 3.92 (95% CI 2.75-5.1; Hedges g 1.15; P<.001). For anxiety, the overall mean difference between the 2 time points was 3.34 (95% CI 2.06-4.61; Hedges g 1.02; P<.001). Further, a moderate effect in improving quality of life was found (g=0.50). Overall, participants were positive about the online intervention and ECoaches (online guidance), and they found the intervention to be culturally appropriate. Conclusions: A culturally adapted, transdiagnostic, internet-based intervention appears to be acceptable and feasible for reducing symptoms of depression, anxiety, or both, and increasing quality of life in university students in Indonesia. Future studies should include a randomized controlled trial to assess the effectiveness of such interventions as they may supplement existing counseling services in universities, reduce the treatment costs, and maximize treatment accessibility in low-resourced settings.