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Arthrospira platensis is an edible blue-green alga that shows beneficial activities in humans and animals. Biotreatment/biotransformation with lactic acid bacteria (LAB) is a popular solution to degrade plant and cyanobacterial cell walls, to produce smaller molecules with enhanced (immunomodulatory, antioxidant, antimicrobial, etc.) properties. Additionally, via peptide bond hydrolysis, LAB proteases yield bioactive peptides with multiple health benefits. In this study, we hypothesized that the Spirulina composition can be improved (by increasing the gamma-aminobutyric acid concentration) during biotreatment with selected LAB strains. However, in addition to desirable compounds, LAB are involved in the processes of biogenic amine (BA) formation. The aim of this study was to investigate the changes in bioactive compounds (L-glutamic acid (L-Glu), gamma-aminobutyric acid (GABA) and BA) during the submerged (SMF) and solid-state (SSF) fermentation of Spirulina with lactobacilli strains (Lacticaseibacillus paracasei No. 244; Levilactobacillus brevis No. 173; Leuconostoc mesenteroides No. 225; Liquorilactobacillus uvarum No. 245). The antimicrobial properties of the untreated and fermented Spirulina against a variety of pathogenic and opportunistic strains (Staphylococcus aureus, Escherichia coli, Acinetobacter baumannii, Staphylococcus haemolyticus, Salmonella enterica, Bacillus cereus, Proteus mirabilis, Klebsiella pneumoniae, Enterococcus faecium and Pseudomonas aeruginosa) were tested. It was found, that most of the fermented Spirulina showed exceptional antimicrobial activity against Staphylococcus aureus but not against the other pathogenic bacteria. The ratios of BA/GABA and BA/L-Glu ranged from 0.5 to 62 and from 0.31 to 10.7, respectively, as well as, the GABA content was correlated with putrescine, cadaverine, histamine, tyramine, spermidine, and spermine contents. Finally, while high concentrations of desirable compounds are formed during fermentation, the formation of non-desirable compounds (BA) must also be considered due to the similar mechanism of their synthesis as well as the possibility of obtaining high concentrations in the end products.