African heritage diets are increasingly being replaced by Western-style dietary patterns because of urbanization, economic development, increased access to processed foods, globalization and changing social norms. The health consequences of this nutrition transition are not well understood. We conducted a randomized controlled trial in the Kilimanjaro region in Northern Tanzania to investigate the immune and metabolic effects of switching between Kilimanjaro heritage-style and Western-style diets for 2 weeks and consuming a traditional fermented banana beverage (‘Mbege’) for 1 week. Seventy-seven young and healthy volunteers assigned male at birth, some living in urban areas and some living in rural areas, were recruited in the trial. Primary outcomes were changes in the immune and metabolic profile before and after the intervention and at the 4-week follow-up. The switch from heritage-style to Western-style diet affected different metabolic pathways associated with noncommunicable diseases and promoted a pro-inflammatory state with impaired whole-blood cytokine responses to microbial stimulation. In contrast, the switch from Western-style to heritage-style diet or consuming the fermented beverage had a largely anti-inflammatory effect. Some of the observed changes in the immune and metabolic profiles persisted at the follow-up, suggesting a sustained impact from the short-term intervention. These findings show the metabolic and immune effects of dietary transitions and the consumption of fermented beverages, underscoring the importance of preserving indigenous dietary practices to mitigate noncommunicable disease risk factors in sub-Saharan Africa. ISRCTN trial registration: ISRCTN15619939.