Dietary fibers such as fructans have beneficial effects on intestinal health but it is unknown whether they impact goblet cells (GCs). Here we studied the effects of inulin-type fructans (ITFs) and graminan-type fructans (GTFs) with different molecular weights on mucus- and endoplasmic reticulum (ER) stress-related genes in intestinal GCs. To that end, GCs were incubated in the presence of ITFs or GTFs, or ITFs and GTFs + TNFα or the N-glycosylation inhibitor tunicamycin (Tm). IL-8 production by GCs was studied as a marker of inflammation. Effects between ITFs and GTFs were compared. We found a beneficial impact of GTFs especially on the expression of RETNLB. GTF II protects from the TNFα-induced gene expression dysregulation of MUC2, TFF3, GAL3ST2, and CHST5. Also, all the studied fructans prevented Tm-induced dysregulation of GAL3ST2. Interestingly, only the short chain fructans ITF I and GTF I have anti-inflammatory properties on GCs. All the studied fructans except ITF I decreased the expression of the ER stress-related HSPA5 and XBP1. All these benefits were fructan-structure and chain length dependent. Our study contributes to a better understanding of chemical structure-dependent beneficial effects of ITFs and GTFs on gut barrier function, which could contribute to prevention of gut inflammatory disorders.