The use of polyphenols in food fortification is a common custom generally carried out to increase its nutritional value. In this paper, ground chili pepper was proposed as a potential functional coffee additive. Various phenolic compounds present in this spice were analyzed by a new, sensitive, and selective ultrahigh-performance liquid chromatography combined with mass spectrometry (UPLC—MS). Separation was done on a column filled with a modified silica gel RP-18, in gradient solvent systems A (1% H3PO4 in water) and B (40% CH3CN in solution A). The capsaicin was found as the main phenolic compound of ground chilli pepper, which concentration was 295.95 mg g−1. It was demonstrated that quercetin is present in this spice also in different forms: not only as dihydrocapsaicin but also as quercetin-3-O-deoxyhexoside-glucuronide and quercetin-3-O-deoxyhexoside, whereas luteolin in the form of three compounds: luteolin-7-O-dihexoside, luteolin-6-C-hexoside-8-C-pentoside, and luteolin-7-O-malonyl-dihexosyl-pentoside. We have also identified apigenin-6-C-hexoside-8-C-pentoside. Furthermore, this paper, for the first time, evaluates the potential bioaccessibility of and interactions between compounds with multidirectional antioxidant properties from coffee and ground chili pepper. All samples, coffee, chili, and a mixture of the two showed ability to scavenge free radicals and chelate iron ions and were characterized by reducing power. The level of these activities changed after simulated gastrointestinal digestion. In the mixtures of water extracts, phytochemicals acted synergistically in the case of five from six tested methods. Interestingly, after digestion, in vitro chili extract lost ability to scavenge O2− radicals; that is why it was impossible to determine the interactions between coffee and chili in this case. Moreover, an antagonism in the action was observed for those cases, where, in water extracts, we have identified synergistic interaction