The impact of the world’s growing population on food systems and the role of dietary patterns in the management of non-communicable diseases underscore the need to explore sustainable and dietary protein sources. Although microalgae have stood out as alternative sources of proteins and bioactive peptides, some species such as Nannochloropsis gaditana remain unexplored. This study aimed to characterize N. gaditana’s proteome and evaluate its potential as a source of bioactive peptides by using an in silico approach. A total of 1955 proteins were identified and classified into functional groups of cellular components, molecular functions, and biological processes. In silico gastrointestinal digestion of identified proteins demonstrated that 202 hydrophobic and low-molecular-size peptides with potential bioactivity were released. Among them, 27 exhibited theorical antioxidant, antihypertensive, antidiabetic, anti-inflammatory, and/or antimicrobial activities. Seven of twenty-seven peptides showed ≥20% intestinal absorption, suggesting potential systemic effects, while the rest could act at local level. Molecular docking demonstrated strong affinities with key enzymes such as MPO, ACE, and DPPIV. Resistance to the digestion, capacity to be absorbed, and multifunctionality were demonstrated for peptide FIPGL. This study highlights N. gaditana’s potential as a sustainable source of novel potential bioactive peptides with promising local and systemic biological effects.

The impact of the world’s growing population on food systems and the role of dietary patterns in the managing of non-communicable diseases underscore the need to explore sustainable and dietary protein sources. Although microalgae have stood out as alternative sources of proteins and bioactive peptides, some species such as Nannochloropsis gaditana remain unexplored. This study aimed to characterize N. gaditana’s proteome and evaluate its potential as a source of bioactive by using an in silico approach. A total of 1955 proteins were identified and classified into functional groups of cellular component, molecular function, and biological process. In silico gastrointestinal digestion of identified proteins demonstrated that 202 hydrophobic and low molecular size-peptides with potential bioactivity were released. Of them, 27 exhibited theorical antioxidant, antihypertensive, antidiabetic, antiinflammatory, and/or antimicrobial activities. Seven of 27 peptide showed ≥20% intestinal absorption, suggesting potential systemic effects, while the rest could act at local level. Molecular docking demonstrated strong affinities with key enzymes such as MPO, ACE, and DPPIV. Resistance to the digestion, capacity to be absorbed and multifunctionality were demonstrated for peptide FIPGL. This study highlights N. gaditana's potential as a sustainable source of novel potential bioactive peptides with promising local and systemic biological effects.