For the discovery of novel drug candidates and bioprobes, it is important to investigate rare natural sources with unique screening methods. Our group tested 1000 original MeOH extracts from natural sources, such as plants and food ingredients using six types of mutant yeasts. In our experiments, Kuji amber was used as the rare domestic natural source and the growth-restoring activity (positive screening) of mutant yeast involving Ca2+-signal transduction was used as a unique screening method. A prominent new anti-allergy compound, named kujigamberol (15,20-dinor-5,7,9-labdatrien-18-ol) was isolated from Kuji amber and known compounds already isolated from modern plants were identified in Baltic and Dominican ambers. Kujigamberol and the methanol extract of Kuji amber (MEKA) exerted inhibitory activity against the degranulation of rat basophilic leukemia-2H3 (RBL-2H3) cells through the inhibition of Ca2+-influx and inhibited the production of leukotriene C4 (LTC4). The effects of kujigamberol and MEKA on rhinitis model were approximately five times more potent than those of the mometasone furoate. Thus, the combination of rare natural sources and unique mutant yeasts can yield valuable bioprobes as novel drug candidates and/or basic research reagents, to benefit humankind.