Peptic and duodenal ulcer diseases are frequently occurring and recurrent gastrointestinal diseases in the world and are usually recurrent, with increasing annual incidence rates. Treatment options are complex, with reported usual nonadherence and probable impairment of quality of life. A cross sectional study was carried out to assess the medication adherence and HRQOL of all ulcer patient who visit the outpatient department of Diete Koko Memorial Hospital, Bayelsa State from January to October 2022, using the MINICHAL and an adapted MMAS-8 scales. The study revealed the participation of more of single females aged between 20 and 40 in rural areas having post-secondary education, with reported income levels below N30, 000.00 monthly. The study also revealed that most of the respondents had their ulcer status diagnosed for more than 4 years before the commencement of this study. Low adherence (3.67) and fair HRQOL (18.9) to peptic and duodenal ulcer therapy was reported. Marital status was not revealed as significant factor of adherence to ulcer treatment but for the HRQOL. Age, education, residence, employment, occupation, income level, and time of diagnosis were reported to be significant predictors of adherence to and HRQOL of peptic and duodenal ulcer medications. Education on treatment of peptic and duodenal ulcer as a means of improving adherence is recommended. The need to investigate in more detail the reasons for poor adherence of use of ulcer medication is urgently recommended.