Medicinal plants have been a traditional remedy for numerous ailments for centuries. However, their usage is limited due to a lack of evidence-based studies elucidating their mechanisms of action. In some countries, they are still considered the first treatment due to their low cost, accessibility, and minor adverse effects. Mexico is in second place, after China, in inventoried plants for medicinal use. It has around 4000 species of medicinal plants; however, pharmacological studies have only been carried out in 5% of its entirety. The species of the Mexican arid zones, particularly in semi-desert areas, exhibit outstanding characteristics, as their adverse growing conditions (e.g., low rainfall and high temperatures) prompt these plants to produce interesting metabolites with diverse biological activities. This review explores medicinal plants belonging to the arid and semi-arid zones of Mexico, focusing on those that have stood out for their bioactive potential, such as Jatropha dioica, Turnera diffusa, Larrea tridentata, Opuntia ficus-indica, Flourensia cernua, Fouquieria splendes, and Prosopis glandulosa. Their extraction conditions, bioactive compounds, mechanisms of action, and biological efficacy are presented, with emphasis on their role in the treatment of respiratory diseases. Additionally, current research, novel applications, and perspectives concerning medicinal plants from these zones are also discussed.