Background: Amlapitta (functional dyspepsia, FD) is experienced as a heterogeneous group of upper abdominal symptoms characterized by upper abdominal colic or discomfort which may also comprise heartburn, bloating, regurgitation, early satiety, anorexia, postprandial fullness, belching, and nausea. Traditional Ayurveda medicines are frequently practiced for FD since long; however, available scientific proof relating to their competence and mechanism of actions are insubstantial. In this article, we report a protocol of a prospective, single-arm, open-label, multicenter clinical study by means of classical Ayurveda formulation to examine the effectiveness, mechanism, and safety of the patients diagnosed with Amlapitta (FD). Materials and methods: Present protocol is a single-arm, open-label multicenter clinical study to find the safety and efficacy of classical Ayurveda formulations Narikela Lavana and Amalakyadi Churna in the management of Amlapitta. A total of 110 patients with Amlapitta will be selected based on the inclusion and exclusion criteria. All the patients will be treated orally; with traditional Ayurveda medicine, i.e., powder Narikela Lavana 2 g, twice daily, before food; and Amalakyadi Churna 3 g, twice daily, after food. The entire participant will undergo 12-week treatment and 2-week follow-up. A total of seven visits will be scheduled for each of the participants, i.e., each one in week 0, 2, 4, 6, 8, 10, and 12. The primary outcomes include changes in FD symptoms in dyspepsia questionnaire; changes in symptoms of Amlapitta disease in Amlapitta symptom rating scale (ASRS) along with satisfactory therapeutic response. The secondary outcomes include disease relapse rate after successful treatment; assessment of quality of life in the participants of FD by the World Health Organization Quality of Life (WHO-QOL) scale; and psychological assessment by Beck's depression inventory scoring scale. Therapeutic mechanism outcomes, safety outcomes, and end-point outcomes will also be assessed. Discussion: Present protocol has been designed with expected better clinical outcome and safety profile in dyspepsia patients in addition to reduce relapse rate of disease during posttreatment period. If found effective, the selected drug will be listed in terms of better efficacy, safety, and cost-effective treatment of Amlapitta. The selected drug may lead to a step ahead of better understanding and management of other gastrointestinal disorders. Trial registration: Trial has been registered REF/2019/07/027369. The registration number for this trial is CTRI/2019/09/021133.