Halophytic plants possess a huge range of active constituents and medicinal benefits. In this study, extracts (water, ethanol, ethyl acetate, dichloromethane, and n-hexane) of two halophytes of the genus Petrosimonia (P. brachiata and P. nigdeensis) were investigated for their phytochemical profiles and pharmacological properties. The phytochemical profiles of both species were investigated using an untargeted metabolomics approach based on high-resolution mass spectrometry. The two species show different polyphenolic profiles and these are influenced by the different extraction solvents used. The same extracts were used for different bioactivity assays. The results show that all extracts yielded total flavonoid and phenolic contents of 11.14–24.22 mg GAE/g and 3.15–22.03 mg RE/g, respectively. While extracts of both species demonstrated a radical scavenging ability in the ABTS assay (16.12–98.02 mg TE/g), only the polar and moderately polar extracts (water, ethanol, and ethyl acetate) showed scavenging potential in the DPPH assay (4.74–16.55 mg TE/g). A reducing potential was also displayed by all extracts in the CUPRAC and FRAP assays (26.02–80.35 mg TE/g and 31.70–67.69 mg TE/g, respectively). The total antioxidant capacity of the extracts ranged from 0.24 to 2.17 mmol TE/g, and the metal chelating activity ranged from 14.74 to 33.80 mg EDTAE/g. The water extracts possessed a higher metal chelating power than the other extracts. All extracts acted as inhibitors of acetylcholinesterase (0.16–3.85 mg GALAE/g) and amylase (0.11–1.28 mmol ACAE/g). Moreover, apart from the water extracts, the other extracts also showed anti-butyrylcholinesterase activity (0.73–2.86 mg GALAE/g), as well as anti-tyrosinase (36.74–61.40 mg KAE/g) and anti-glucosidase (2.37–2.73 mmol ACAE/g) potential. In general, the water extracts were found to be weak inhibitors of the tested enzymes, while the ethanol extracts mostly showed an inhibitory effect. The obtained findings revealed the antioxidant and enzyme inhibitory properties of these two species and demonstrated that the solvent type used affected the pharmacological properties of the extracts and hence, can be useful to further investigate the active constituents yielded in the extracts and understand the mechanisms involved.