Hydrogenated fat-embedded calcium gluconate (HFCG), a prebiotic mixture designed to target the hindgut, has improved milk and component yields when supplemented in mid-lactation cows, likely due to improved hindgut health. The objective of this study was to evaluate production responses to HFCG when fed to dairy cattle over a full lactation. Seventy-four Holstein cows (21 primiparous, 53 multiparous) were used in a randomized complete block design comparing supplementation with HFCG (approximately 16 g/day supplement delivering approximately 6.4 g active ingredient) to a negative control from approximately 21 days prior to calving until end of lactation. In multiparous cattle supplemented with HFCG, average daily milk protein yield ( P = 0.037) was increased during the first 8 weeks of lactation, while average daily yields of milk fat, and fat- and energy-corrected milk tended ( P ≤ 0.075) to increase over the same period of time. Increased yields were likely supported by the concurrent increase in dry matter intake ( P = 0.036). Future work is needed to characterize the mode of action of this product within both the hindgut lumen and host, as well as investigate the potential differential responses between primiparous and multiparous animals over the course of lactation.