Asthma is a chronic respiratory disease produced by an aberrant immune response that originates with breathing difficulties and cough, through airway remodeling. The above pathophysiological events of asthma emerge the regulators of effectors, like epigenetics, which include microRNAs (miRNAs) who perform post‐transcriptional regulation, controlling diverse pathways in respiratory diseases. The objective of the study was to determine how miR‐185‐5p regulates the secretion of periostin by airway structural cells, and smooth muscle cells contraction, both related to airway remodeling in asthma. We used miR‐185‐5p mimic and inhibitors in bronchial smooth muscle cells (BSMCs) and small airway epithelial cells (SAECs) from healthy subjects. Gene expression and protein levels of periostin (POSTN), CDC42, and RHOA were analyzed by RT‐PCR and ELISA/Western blot, respectively. BSMC contractility was analyzed using cell‐embedded collagen gels and measurement of intracellular calcium was performed using Fura‐2. Additionally, miR‐185‐5p and periostin expression were evaluated in sputum from healthy and asthmatics. From these experiments, we observed that miR‐185‐5p modulation regulates periostin mRNA and protein in BSMCs and SAECs. A tendency for diminished miR‐185‐5p expression and higher periostin levels was seen in sputum cells from asthmatics compared to healthy, with an inverse correlation observed between POSTN and miR‐185‐5p. Inhibition of miR‐185‐5p produced higher BSMCs contraction induced by histamine. Calcium mobilization was not modified by miR‐185‐5p, showing that miR‐185‐5p role in BSMC contractility is performed by regulating CDC42 and RhoA pro‐contractile factors instead. In conclusion, miR‐185‐5p is a modulator of periostin secretion by airway structural cells and of smooth muscle contraction, which can be related to asthma pathophysiology, and thus, might be a promising therapeutic target. In this study, we show that miR‐185‐5p, which is inversely correlated to POSTN expression in sputum from the asthmatic and healthy, is able to modulate periostin secretion by airway structural cells such as epithelial and smooth muscle cells, of crucial importance in airway remodeling, while also being able to regulate the synthesis of RhoA and CDC42 protein levels, which increase smooth muscle contractile capacity. These events are the key mechanisms involved in the development and maintenance of the symptoms of asthma.