Changes in land use and climate change have been reported to reduce biodiversity of the environment and human microbiota. This may lead to inadequate and unbalanced stimulation of immunoregulatory circuits and ultimately, to clinical diseases, such as asthma and allergies. We summarised available empirical evidence on the role of inner and outer layers of biodiversity in the development of asthma, asthma-like symptoms, and allergic sensitization. We conducted a systematic search in SciVerse Scopus, PubMed MEDLINE, and Web of Science up to 5 December 2022 to identify relevant studies assessing the relations between inner and outer layers of biodiversity and the risk of asthma, wheezing and/or allergic sensitization. We applied random-effects models to calculate summary effect estimates. The protocol was registered in PROSPERO (CRD42022381725). Of 75 studies, 20 provided effect estimates for the meta-analysis showing an association between high outer layer biodiversity and a low risk of asthma development (Shannon diversity index: OR (95% CI) = 0.77 (0.55; 1.06); bacterial richness: OR (95% CI) = 0.74 (0.57; 0.96)). Although the evidence on the effect of inner layer biodiversity suggested that bacterial diversity was slightly higher among individuals with asthma, there was no clear evidence of a significant association between inner layer biodiversity and the risk of asthma, wheezing or allergic sensitization. The weight of evidence suggests that environmental exposure to high biodiversity may protect from the development of asthma, whereas there was no consistent evidence on any association between inner layer biodiversity and asthma, wheezing or allergic sensitization.