Given the role of the intestinal microbiota in obesity and related disease, strategies to modulate the composition of the intestinal microbiota may augment traditional weight-management approaches. Here, we examined the safety and tolerability of 28 days of supplementation with bovine whey-derived lactoferrin and immunoglobulin supplements in a cross-sectional cohort of free-living adults. Participants (n = 20 each group) received enteric-coated whey-derived bovine lactoferrin (200 mg), immunoglobulin (200 mg or 800 mg), combination lactoferrin/immunoglobuiln supplements (200 mg/200 mg, 200 mg/800 mg) or placebo in a double-blind design. Supplement use was generally well tolerated and routine haematology, and clinical chemistry measures were largely unchanged following supplementation. Measures of body composition remained stable and indices of glycaemic control and blood lipids revealed fluctuations of <5% but were not significantly different between groups. Overall, short-term lactoferrin/immunoglobulin supplementation was well tolerated in this cohort; use of these types of supplements to enhance other weight management strategies should be investigated over extended periods.