INTRODUCTION: Evidence is emerging of complex interactions occurring between gastrointestinal (GI) parasites of ruminants and the resident gut flora, with likely implications for the pathophysiology of worm infection and disease. Similarly, recent data point toward the occurrence of a GI nematode (GIN)-specific microbiota, with potential roles in worm fundamental physiology and reproduction. Parasite-microbiota relationships might represent potential targets for the development of novel parasiticides. AREAS COVERED: In this article, we review current knowledge of the role(s) that host- and helminth-associated microbiota play in ruminant host-parasite relationships, and outline potential avenues for the control of GIN of farmed ruminants via the manipulation of resident microbial species with putative functions in infection establishment, host-immune modulation, and/or parasite fitness and survival. EXPERT OPINION: In order for this knowledge to be translated into practical applications, we argue that several aspects of the nematode-microbiota cross-talk must be addressed, including (i) the causality of interactions between the parasite, the gut microbiota, and the host immune system, (ii) the modes of action of dietary prebiotics and probiotics, (iii) the mechanisms by which diet supplementation aids the development of resistance/tolerance to GI helminth infections and (iv) the composition of the GIN microbiome and its role(s) in parasite biology and physiology.