In this study, aerial part and root extracts of two Silene species, S. caramanica and S. otites obtained by five extraction methods (homogenizer assisted, maceration, Soxhlet, and ultrasound assisted extractions and infusion) were screened for their phytochemical contents, antioxidant and anti-enzymatic properties. Spectrophotometric assays revealed the extracts to possess total phenolic and flavonoid contents in the range of 13.28–47.18 mg gallic acid equivalent (GAE)/g dry extract and 0.22–42.56 mg rutin equivalent (RE)/g dry extract, respectively for S. caramanica and 13.97–21.35 mg GAE/g and 0.40–42.87 mg RE/g, respectively for S. otites. The aerial part extracts obtained by homogenizer assisted extraction of both plants were found to yield the highest phytochemical contents compared to the other extracts. HPLC analysis revealed quinic acid to be present in the highest quantity in the extracts. In DPPH and ABTS assays, the extracts demonstrated the highest free radical scavenging property (14.22–48.25 and 24.88–107.60 mg trolox equivalent (TE)/g dry extract, respectively), reducing activity in CUPRAC and FRAP assays (38.60–175.85 and 31.43–108.72 mg TE/g dry extract, respectively). While all extracts exhibited anti-acetylcholinesterase (0.69–2.56 mg galantamine equivalent (GALE)/g dry extract), anti-butyrylcholinesterase (0.80–2.50 mg GALE/g dry extract) activity displayed by only the aerial part/Soxhlet extract of S. caramanica, all root extracts of S. caramanica, and all the extracts of S. otites except their infusion extracts (0.80–2.50 mg GALAE/g dry extract). The extracts were also found to inhibit tyrosinase (2.36–20.95 mg kojic acid equivalent (KAE)/g dry extract), alpha-amylase (0.11–0.46 mmol acarbose equivalent (ACAE)/g dry extract), and with the exception of the root/infusion extracts, were also found to act as inhibitors of alpha-glucosidase (0.03–0.41 mmol ACAE/g dry extract). Taken together, this study revealed these two Silene species to act as antioxidants and enzyme inhibitors and the findings are in favor for more advanced studies to be carried out to confirm their pharmacological properties.