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The main objective of this work was to evaluate the combined effect of a biotechnology process, based on selected yeast strains, and a high-pressure homogenization (HPH) treatment on the microbiological quality, structural organization of proteins, chitin content, and antioxidant activity of a mixture of cricket powder (<i>Acheta domesticus</i>) and water. Compared to untreated samples, the cricket matrix treated with HPH four times at 180 MPa promoted the growth of the inoculated <i>Yarrowia lipolytica</i> and <i>Debaryomyces hansenii</i> strains. HPH did not affect the concentration of chitin; however, the combination with microorganisms tended to reduce the content. Although the antioxidant activity increased from 0.52 to 0.68 TAC mM/TE after a 48 h incubation in the control, it was further improved by the combination of HPH and <i>D. hansenii</i> metabolism, reaching a value of 0.77 TAC mM/TE. The combination of the two approaches also promoted a reduction in the intensity of bands with molecular weights between 31 and 21.5 kDa in favor of bands with a lower molecular weight. In addition, HPH treatment reduced the number of accessible thiols, suggesting protein structure changes that may further impact the technological properties of cricket powder.