Abstract Purpose Evaluation of a lozenge for targeted micronutrition (holo-BLG), a new invention based on the farm effect, in house dust mite (HDM) allergic rhinoconjunctivitis (ARC) patients in a standardized allergen exposure chamber (AEC). Methods Eligible HDM allergic patients were exposed to HDM raw material in an AEC for 120 min before (V1) and after (V3) 3 months of holo-BLG supplementation. Nasal, conjunctival, bronchial and other symptoms were rated by the patients every 10 min and, wellbeing, peak nasal inspiratory flow (PNIF), and lung function parameters every 30 min. Primary endpoint was the change in median Total Nasal Symptom Score (TNSS) at V3 compared to V1 at 120 min of exposure. Secondary endpoints consisted of the exploratory analysis of the temporal evolution of symptom scores using linear mixed effects models. Results A total of 32 patients were included in the analysis. A significant improvement of 60% (p = 0.0034) in the primary endpoint TNSS (V1 2.5 [interquartile range, IQR 1–4], V3 1.0 [IQR 1–3]) was observed. 40% improvement was seen for the Total Symptom Score (V1 5.0 [IQR 3–9], V3 3.0 [IQR 2–4]; [Wilcoxon test: confidence interval 1.5–4.0, p < 0.0003]). The analysis of the temporal evolution of all symptom scores and the personal wellbeing revealed clinically meaningful improvement over time, manifested in a lower symptom increase during the final HDM exposure. No relevant differences were observed for PNIF and lung function parameters. Safety and tolerability were rated as excellent. Conclusions The effect of holo-BLG resulting in immune resilience might help to fight the allergy epidemic on a new front based on targeted micronutrition of immune cells. Trial registration The study was retrospectively registered at clinicaltrials.gov (NCT04477382).