Safflower (Carthamus tinctorius L.), which belongs to the Compositae family, has been utilized traditionally for food coloring and as an additive for food, healthy beverages and cosmetics in many countries (Salem et al., 2014;Jia-Xi et al., 2019). A wide variety of glycosides has been isolated from the dried flowers of C. tinctorius used as a traditional medicinal plant (Zhang et al., 2019). C. tinctorius has been identified to consist of more than 200 compounds including flavonoids, alkaloids, lignans, alkane diols, riboflavin, steroids and quinochalcone C-glycosides (Li et al., 2017).Flower petals contain three dyeing pigments: Safflower yellow A, safflower yellow B, and red (Carthamin). Compared to carthamin (red), large quantities of yellow pigments are present in safflower. Additionally, safflower yellow pigments are more stable than carthamin under ultraviolet (UV) light (Elshemy et al., 2019). In other words, the main active ingredients which can be extracted from dried petals of safflower could be stated as two main types. These are major red pigments named carthamin, which are water-insoluble, and major yellow pigments named hydroxysafflor yellow A and safflor yellow B, which are watersoluble (Jadhav & Joshi, 2015). Thus, C. tinctorius is used as a dyestuff in the food and textile industry, and it is frequently used for adulteration instead of saffron (Villa et al., 2017). Moreover, synthetic dyes and antioxidants have wide use in the food industry. Consumer preferences have been directed towards natural dyes and antioxidants because of safety concerns and their helpful effects against certain diseases, such as neurodegenerative disorders, cancer, aging, diabetes and coronary heart disease (Karimkhani et al., 2016). Thus, natural colorants from plant pigments are being explored and analyzed as alternatives or replacements for synthetic food colorants. In general, consumers are concerned about the safety of foods that contain synthetic ingredients. Safflower is safe for use in foods and has a wide range of biological activities including antioxidant, antimicrobial (Salem et al., 2011), anti-anxiety, antidepressant (Qazi et al., 2015, anticoagulant (Wang et al., 2014), antitumor (Luo et al., 2015 and anti-osteoporosis (Choi et al., 2010) effects.When medicinal plants and their phenolic extracts are consumed, they undergo a digestive process in the intestines. In vitro digestion models are considered to be simple, fast, inexpensive, safe and repeatable tools to evaluate the digestive stability of diverse food components and have been improved as another approach to in vivo studies. They also do not have the same ethical restrictions as many in vivo methods (Gunathilake et al., 2018). Therefore, it is significant to determine how the digestive process affects the stability and antioxidant activities of phenolic compounds.