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Arthrospira platensis is a sustainable microalga enriched with phenolic compounds and carotenoids—bioactives associated with antioxidant and potential neuroprotective effects. Their efficacy depends on more than extraction yield; digestive stability and intestinal absorption also play key roles, particularly when considering systemic effects potentially mediated by the gut–brain axis. Importantly, bound phenolics remain underexplored in many food matrices. This study aimed to optimize green extraction approaches for both free and bound phenolics and carotenoids from A. platensis, and to evaluate their digestive bioaccessibility and intestinal permeability as key indicators of their systemic delivery potential, including possible implications for gut–brain axis modulation. Three aqueous extraction methods—conventional solvent extraction, ultrasoundassisted extraction (UAE), and microwave-assisted extraction (MAE)—were tested and optimized based on total phenolic content (TPC) and antioxidant activity (DPPH, ABTS). Bound phenolics were liberated via acid and alkaline hydrolysis. The most promising extract (MAE) underwent standardized in vitro digestion (INFOGEST 2.0), followed by Caco-2 permeability assays. Individual aminoacids, phenolic compounds and carotenoids were identified and quantified across digestion stages via HPLC-DAD. MAE achieved the highest TPC (2.94 ± 1.18 mg GAE/g DW), with bound phenolics contributing an additional 2.86 ± 0.42 mg GAE/g DW. Digestive simulation led to enhanced phenolic release in the intestinal phase (6.18 ± 0.54 mg GAE/g DW), with syringic, gallic, and caffeic acids dominating the profile. In contrast, carotenoids such as β-carotene and zeaxanthin showed reduced stability during gastric digestion, limiting their bioaccessibility. Caco-2 assays revealed moderate permeability of phenolics, suggesting capacity for systemic absorption—a prerequisite for interactions along the gut– brain axis. This work demonstrates the potential of A. platensis as a multifunctional bioactive source, with optimized extraction and digestive behavior of phenolics supporting future exploration of neuroprotective pathways via the gut–brain axis. The limited carotenoid bioaccessibility reinforces the need for protective formulation strategies. These findings offer a foundation for developing functional foods tailored toward systemic and cognitive health.