Citrus (mandarin and orange) pomace is an agro-food industrial waste enriched in polyphenols and dietary fiber with great potential as a functional ingredient. In this work, the chemical composition and in vitro bioaccessibility of health promoting compounds present in raw citrus (Clemenule and Ortanique mandarins and Navel and Valencia oranges) pomaces were studied. In addition, the by-products were employed as food ingredients in cookies and the effect of the food matrix on the bioaccessibility of the bioactive compounds was evaluated. Nobiletin, hesperidin/neohesperidin, tangeretin, heptamethoxyflavone, tetramethylscutellarein, and naringin/narirutin were detected in the citrus samples by UHPLC-MS. Citrus pomaces were in vitro digested mimicking the human oral gastrointestinal conditions and the bioactivity of the digests (antioxidant, carbohydrases modulation and anti-inflammatory effects) was assessed. The bioaccessibility of the antioxidants in the by-products was confirmed by TPC (6.6-11.0 mg GAE/g digest), ABTS (65.5-97.1 µmol TE/g digest), ORAC-FL assays (135.5-214.8 µmol TE/g digest), and inhibition of ROS formation induced by treatment with tert-butylhydroperoxide 1 mM in intestinal IEC-6 (19-45%) and CCD-18Co (28-45 %) cells pretreated with the digests at concentrations ranging between 5 and 25 µg/mL. Inhibitors of the α-glucosidase (IC₅₀ 3.97-11.42 mg/mL) and α-amylase (IC₅₀ 58.04-105.68 mg/mL) also remained bioaccessible after in vitro digestion of citrus pomaces. In addition, the bioaccessible compounds in orange pomace samples significantly reduced (p<0.05) the LPS-induced NO production in RAW264.7 macrophages. The digests of orange pomace cookies with the nutrition claims “no-added sugars” and “source of fiber” presented antioxidant and antidiabetic properties, and good sensory quality (6.86-6.68 in a scale of 1 to 9). The results support the feasibility of unfractionated orange pomace as functional ingredients for diabetes prevention/treatment. The health promoting benefits observed in the present research may be at least partially associated to flavonoids.