A green and innovative method, manothermosonication (MTS), for proteins extraction from dry Arthrospira platensis cyanobacteria assisted by ultrasound was designed in this work. Manothermosonication (probe, 20 kHz) was compared to a conventional process performed in the same conditions without ultrasounds. The extraction was carried out with a continuous flow rate at 15 mL/hour. Extraction parameters were optimized using a central composite design. Moreover, mathematic modelling and microscopic investigations were realized to allow a better understanding of ultrasound physical and structural effects on spirulina filaments and mass transfer phenomena over time. Crude extract and sections stained with toluidine blue were analyzed with optical and scanning electron microscopies. According to experimental results, MTS promoted mass transfer (high effective diffusivity, De) and enabled to get 229% more proteins (28.42 ± 1.15 g/100 g DW) than conventional process without ultrasound (8.63 ± 1.15 g/100 g DW). With 28.42 g of proteins per 100 g of dry spirulina biomass in the extract, a protein recovery rate of 50% was achieved in 6 effective minutes with a continuous MTS process. Microscopic observations showed that acoustic cavitation impacted spirulina filaments by different mechanisms such as fragmentation, sonoporation, detexturation. These various phenomena make extraction, release and solubilization of spirulina bioactive compounds easier.