This study evaluated a therapeutic diet high in eicosapentaenoic (EPA) and docosahexaenoic acid (DHA) of marine source (EPA:DHA ratio 0.69:1), turmeric extract, and hydrolysed collagen in cats (N = 30) with naturally occurring osteoarthritis (OA) over a 13-week (W) period, followed by a 4-W washout, using four previously validated pain/functional outcomes. Compared to the placebo diet, the therapeutic diet significantly improved peak vertical force (p = 0.017; W16, 64% responders), correlating to enhanced weight bearing; stair assay compliance (p < 0.001; W16, 87% responders), reflecting reduced fatigue related to OA pain; night-time actimetry (cohort effect; p = 0.05, 67% responders), suggesting greater spontaneous mobility and comfort; and MI-CAT(V) score (cohort effect; p < 0.001, 80% responders), indicating reduced functional impairments. The earliest therapeutic response was observed at W06, marked by an inflection point between actimetric linear regressions of both cohorts, confirmed by significant MI-CAT(V) differences (p < 0.007; W08; W12; W16). The MI-CAT(V) clinical metrology instrument was validated for inter-rater reliability, minimal placebo effect (<15% responders), and OA severity clustering. Despite baseline differences in biomechanical assessments (p < 0.05), both moderate and severe OA clusters responded equally positively to the therapeutic diet. Based on all outcomes, the therapeutic diet showed promise for the long-term management of feline OA, with no observed side effects.