Introduction <p>Maternal anemia is a major public health concern in Ethiopia. Nutrient-dense local foods like amaranth may improve iron status during pregnancy. This study evaluated adherence, safety, bioavailability, and acceptability of amaranth grain flatbread during pregnancy in Sidama region, Ethiopia.</p> Methods <p>Between September 2024 and February 2025, a two-arm parallel cluster randomized controlled trial was carried out in the Hawela Lida district, Ethiopia. A total of 306 pregnant women (&lt; 12&#xa0;weeks gestation) were randomized to amaranth (<i>n</i> = 153) and maize flatbread (<i>n</i> = 153) for six months. Primary outcomes: haemoglobin concentration and iron deficiency anemia (IDA). Secondary outcomes: adherence, safety, bioavailability biomarkers, and acceptability. Blood samples were analyzed using HemoCue and ELISA. Mixed-effects models accounted for clustering and baseline covariates.</p> Results <p>Of 306 participants, 293 (95.8%) completed the study. The amaranth group had higher mean haemoglobin concentration (adjusted β = + 2.67, 95% CI: 2.41–2.91) and lower IDA (ARR = 0.47, 95% CI: 0.26–0.84) than controls. Adherence was higher in amaranth arm (AOR = 1.25, 95% CI: 1.08–1.44) and no serious adverse events occurred. Acceptability was greater in the intervention arm (AOR = 1.72, 95% CI: 1.21–2.46). Qualitative results supported quantitative findings, with participants reporting enthusiasm and readiness to continue consuming.</p> Conclusion <p>Daily amaranth flatbread is safe, highly acceptable, and improves maternal iron status, supporting its integration into maternal nutrition programs in low-resource settings.</p> Trial registration <p>ClinicalTrials.gov, NCT06536153, registered on July 30, 2024.</p>