Advances in lipidomics revealed the crucial role of fatty acids in physiological and pathological conditions. Imbalances in fatty acid biodistribution might drive the development of canine cognitive dysfunction (CCD), a disabling disease requiring multidisciplinary treatments. There is a growing focus on nutraceuticals, being adjuvant therapies with negligible adverse events. This paper evaluates the effect of Neurogen Pet Ultra ® supplementation in aging dogs with CCD. Twenty-four CCD dogs were administered with Neurogen Pet Ultra ® for 60 days, followed by 60 days without supplementation. The erythrocyte membrane lipidome was examined in all 24 dogs at the study entry while in the 12 patients who completed the study, even at days 60 and 120. A cluster of 10 fatty acids was quantitatively analyzed using gas chromatography. Diseased dogs' fatty acid values were statistically compared with those of 8 senior healthy dogs. Dogs with CCD displayed alterations of the fatty acid profile, mainly represented by the increase of saturated and monounsaturated fatty acid families (p = 0.0011 and 0.0194, respectively) and the decrease of the polyunsaturated family (p = 0.0009). Nutraceutical supplementation resulted in a statistically significant normalization of the content of nearly all fatty acids. Lipid modifications in treated dogs were evaluated throughout the follow-up period, showing marked improvements over time. The capability of Neurogen Pet Ultra ® to remodel the lipid imbalance confirms its favorable effect on CCD dogs. Moreover, these findings provide new tools for an accurate disease diagnosis, along with the validation of an unbiased method to monitor any therapy.