This study focused on the quality loss inhibition of fish muscle during refrigerated storage. Two parallel experiments were carried out that were focused on the employment of pitaya (Stenocereus thurberi) extracts in biodegradable packing films. On the one hand, a pitaya–gelatin film was employed for hake (Merluccius merluccius) muscle storage. On the other hand, a pitaya–polylactic acid (PLA) film was used for Atlantic mackerel (Scomber scombrus) muscle storage. In both experiments, fish-packing systems were stored at 4 °C for 8 days. Quality loss was determined by lipid damage and microbial activity development. The presence of the pitaya extract led to an inhibitory effect (p < 0.05) on peroxide, fluorescent compound, and free fatty acid (FFA) values in the gelatin–hake system and to a lower (p < 0.05) formation of thiobarbituric acid reactive substances, fluorescent compounds, and FFAs in the PLA–mackerel system. Additionally, the inclusion of pitaya extracts in the packing films slowed down (p < 0.05) the growth of aerobes, anaerobes, psychrotrophs, and proteolytic bacteria in the case of the pitaya–gelatin films and of aerobes, anaerobes, and proteolytic bacteria in the case of pitaya–PLA films. The current preservative effects are explained on the basis of the preservative compound presence (betalains and phenolic compounds) in the pitaya extracts.