Pteridaceae is the most ethnomedicinally significant fern family among pteridophytes. This family possesses numerous phytochemically sound and potent species. There are 58 species altogether that bear the potential to treat a great number of human ailments. Traditional ethnic minorities staying in a remote locality hold indigenous wisdom helping us to get enlightened about the significance of traditional knowledge of plants. Since the ancient day’s Adiantum capillus-veneris, a species from the family Pteridaceae was used as an Indian herb-based medicine mentioned in Samhitas. An insight phytochemical analysis unwrapped the presence of iso-adiantol, rutin, quercetin, and iso-adiantone in this species, which act as an anticoagulant, antipyretic, and antivenom against wounds, fever, and snake bites, respectively. Further, a number of genera – Acrostichum, Actiniopteris, Aleuritopteris, Antrophyum, Ceratopteris, Cheilanthes, Cheilosoria, Coniogramme, Doryopteris, Hemionitis, Notholaena, Onychium, Parahemionitis, Pityrogramma, Pteris, and Vittaria – elongate the list revealing the essence of family Pteridaceae being pharmacologically active possessing rich secondary metabolites, such as tannins, saponins, cardiac glycosides, sterols, oils, flavonoids, quinones, glycosides, terpenoids, phenol, coumarins, steroids, alkaloids, anthocyanin, and betacyanin addressing a variety of severe human ailments like diarrhea, fever, bronchitis, tuberculosis, uterine problem, wounds, sprains, typhoid, bone fractures, blood pressure, helminthiasis, and rheumatism and a plethora of ailments and health disorders. This chapter emphasizes the various phytochemicals present in all medicinally important known species of the Pteridaceae family which are pharmacologically active against numerous human disorders. © 2023, Springer Nature Switzerland AG.