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Abstract Background Type 2 diabetes mellitus (T2DM) is a chronic medical condition affecting more than 95% of people with diabetes. Traditionally, some medicinal plants have been considered as an effective approach in management of T2DM. This trial evaluated the effects of date seed powder (DSP) on glycemia indices and oxidative stress in T2DM patients. Methods In this trail, 43 patients with T2DM were randomized to two groups: either 5 g/d of the DSP or placebo for 8 weeks. Levels of glycemic indices, lipolpolysaccharide (LPS), and soluble receptor for advanced glycation end products (s-RAGE), as well as other parameters associated with oxidative stress were assessed at baseline and after 8 weeks. Independent t-test and analysis of covariance (ANCOVA) were used for between-groups comparisons at baseline and the post-intervention phase, respectively. Results The results showed that supplementation with DSP significantly decreased HbA1c (−0.30 ± 0.48%), insulin (−1.70 ± 2.21 μU/ml), HOMA-IR (−1.05 ± 0.21), HOMA-B (−0.76 ± 21.21), lipopolysaccharide (LPS) (−3.68 ± 6.05 EU/mL), and pentosidine (118.99 ± 21.67 pg/mL) (P |