Guar gum-derived galactomannan (GGGM) has been widely used in the food industry for a long time and its adverse impacts have been scarcely reported. Galactomannan is considered to have a structure similar to the surface components of certain pathogens, and the present study was thus conducted to investigate if oral administration of GGGM could cause physiological effects that were hypothesized to be related to intestinal inflammatory responses. The results showed that oral administration of GGGM resulted in compromises on growth performance, an increase of the relative weight of spleen and epididymal fat, and an elevation of the α1-acid glycoprotein content in both serum and livers of mice. With regard to energy metabolism-related indices, the activities of intestinal lactic dehydrogenase and succinic dehydrogenase were all increased by the GGGM treatment in both in vivo and in vitro experiments, the latter of which also showed an elevation in the consumption of reducing sugar by intestinal epithelial cells along with a reduced viability of these cells in response to the GGGM treatment. Notably, the GGGM treatment triggered intestinal inflammatory responses that were evidenced by the increased expression of intestinal inflammatory cytokines such as TNF-α and IL-6 both in vivo and in vitro, which were at least partially responsible for the increased energy expenditure in the intestine and the retardation of growth. The results of this study could expand our knowledge of GGGM administration and provide integrated insights into the consumption of GGGM-containing foods.