This study evaluated PYM00217, a proprietary blend of plant extracts, in the management of canine atopic dermatitis (AD). One hundred and twenty dogs were diagnosed with perennial AD on the basis of history, clinical signs, a positive test for perennial allergens and elimination of other dermatoses. Exclusion criteria included antimicrobials within 7 days, antihistamines within 14 days, oral/topical glucocorticoids or ciclosporin within 28 days, and parenteral glucocorticoids, essential fatty acids or immunotherapy within 56 days. Flea control, shampoos and ear cleaners were permitted. Dogs with a minimum canine atopic dermatitis extent and severity index (CADESI) of 25 were randomly allocated to receive PYM00217 (100, 200 or 400 mg kg−1 day−1) or placebo for 12 weeks. The mean reductions in CADESI (intention-to-treat population) were 3.9% (placebo; n = 29), 4.4% (100 mg kg−1 day−1; n = 30), 23.4% (200 mg kg−1 day−1; n = 29) and 8.5% (400 mg kg−1 day−1; n = 29). The reduction in the 200 mg kg−1 day−1 group was significant (P < 0.01). For dogs with a baseline CADESI ≥ 50, the mean changes were +10.6% (placebo; n = 12), +0.6% (100 mg kg−1 day−1; n = 14), −29.3% (200 mg kg−1 day−1; n = 14) and −3.4% (400 mg kg−1 day−1; n = 15). The 200 mg kg−1 day−1 dose was significantly more effective than placebo (P = 0.038). No serious adverse effects were reported. Minor adverse effects seen in 10% (placebo and 100 mg kg−1 day−1), 24% (200 mg kg−1 day−1) and 42% (400 mg kg−1 day−1) of cases were mainly minor gastrointestinal disorders and only five cases required cessation of dosing. Two dogs (one in each of the 100 mg kg−1 day−1 and 200 mg kg−1 day−1 groups) refused to eat the medicated food. In conclusion, PYM00217 at 200 mg kg−1 appears to be an effective, palatable and well-tolerated treatment for canine AD.