The peaceful phenomenon of the co-evolution between the prokaryotes (microbiota) and the eukaryotes (parasites including protozoa and helminths) in the animal gut has drawn the researchers' attention. Importantly, exploring the potential of helminths for therapeutic uses was one of the reasons behind understanding the physiological and immunological crosstalk existing between them. Here we discuss the interactive immunological associations of helminths and microbial responses individually and in combination with their hosts. Considering that there is probably crosstalk between eukaryotic organisms like helminths and protozoa with their host's gut microbiota, in this review we searched the literature identifying the privileged and favourable relationship generated between them in the host. Understanding the possibilities of the role of helminths along with gut microbiota as a black box would certainly help decode the therapeutic intrusion with helminths in experimental clinical trials, and a successful trial could be used to consider possible future and safe treatments for various immune-inflammatory diseases in humans.