Chia seeds present with an excellent nutrient profile, including polyunsaturated fat, protein, fibre and bioactive compounds, which make them a potential food or ingredient to bring beneficial health effects. However, their tough structure could mean that these seeds remain hardly disrupted during digestion, thus preventing the release and digestibility of nutrients. In the present study, different chia products (seeds, whole flour, partially defatted flour and sprouts) were assessed in terms of proteolysis, lipolysis, calcium and polyphenols bioaccessibility and antioxidant activity. In vitro digestions were performed supporting standard intestinal (pH 7, bile salts concentration 10 mM) and altered (pH 6, bile salts concentration 1 mM) conditions. The altered conditions significantly reduced lipolysis, but not proteolysis. Regarding the food matrix, compared to the chia seeds, whole and partially defatted flour increased the hydrolysis of lipids and protein, relating to reduced particle size. Sprouting had an enhancing effect on proteolysis but prevented lipolysis. Calcium bioaccessibility dropped in all the samples in the two intestinal conditions. The digestion process led to increased polyphenols bioaccessibility in all the structures, but reduced antioxidant activity except in the milled structures. In conclusion, milling should be applied to chia seeds prior to consumption in cases where enhancing the potential uptake of macro and micronutrients is targeted, and sprouting is suitable to enhance protein digestibility and reduce lipolysis.