The pomegranate is an emerging functional food which is nowadays becoming more and more commercially attractive. Each part of this fruit (peels, arils and seeds) has a specific phytocomplex, rich in anti-oxidant and anti-radical compounds. Among these, punicalagin and ellagic acid continue to be widely studied for their numerous beneficial effects on human health (anti-inflammatory effects, anti-diabetes activity, cardio-protection, cancer prevention). Despite their exceptionally valuable composition and high adaptability to different climatic conditions, pomegranate fruits are highly susceptible to splitting during different stages of ripening, so much so that an estimated 65% of the production may be lost. A “zero-kilometer” approach should therefore be adopted to utilize such a valuable product otherwise destined to be downgraded or even incinerated, with a very high environmental impact. The aim of this work is to highlight and compare the compositional differences between whole and split pomegranates belonging to the cultivar Dente di Cavallo, grown in Apulia (Italy), to assess a valuable role for this split fruit usually considered as waste. The arils and peels are subjected to extraction procedures and the extracts analyzed by CIEL*a*b*, HPLC-DAD and HS-SPME/GC-MS. Moreover, an assessment of the inhibitory activity against α-glucosidase, acetylcholinesterase and tyrosinase enzymes has also been applied. The data show a better chemical profile in split fruits (namely 60% more anthocyanin content than intact fruit) with very interesting results in terms of α-glucosidase inhibition. The juices obtained by squeezing are also compared to commercial juices (“Salus Melagrana” and “La Marianna”) processed from the same cultivar and subjected to the same protocol analysis.