Piccolo begins as the reincarnation and final offspring of the villainous King Piccolo, inheriting his father's quest for world domination and vengeance against Son Goku. This drive defines his early role as a primary antagonist during the final saga of the original series, culminating in brutal combat against Goku at the 23rd World Martial Arts Tournament. Following his defeat, an uneasy alliance forms with Goku to confront greater threats, starting with the Saiyan Raditz, marking the start of his shift from outright villainy.

A pivotal change occurs when Piccolo undertakes training Goku's young son, Gohan, for the Saiyan invasion. Initially pragmatic, this responsibility fosters an unexpected bond, culminating in Piccolo sacrificing his life to save Gohan against Nappa. This act cements his transformation into a permanent ally and Earth protector. His evolution continues through significant fusions: merging with the Namekian warrior Nail on planet Namek amplifies his power sufficiently to challenge Frieza's second form, while later assimilating with Kami, his benevolent counterpart, restores their original identity as the Nameless Namekian. This fusion integrates Kami's wisdom and knowledge, enabling Piccolo to confront the Android threat and achieve a state known as "Super Namek." These unions blend aspects of their personalities, making him more strategic and articulate in battle.

Piccolo possesses a stern, analytical demeanor, valuing solitude and meditation. He demonstrates pragmatic combat strategy, often exploiting opponents' weaknesses over brute strength. His tactical mind and willingness to collaborate, even with former rivals, become hallmarks. His relationship with Gohan endures beyond training, evolving into a familial bond where he acts as a surrogate uncle to Gohan's daughter, Pan, frequently assisting with routines like school pickup.

His abilities derive from Namekian physiology: limb regeneration, superhuman senses, flight, and energy projection. Signature techniques include the Makankōsappō (Special Beam Cannon), a concentrated piercing beam; the Renzoku Sen Kōdan (Hellzone Grenade), involving strategically placed energy orbs; the Gekiretsu Kodan (Light Grenade); and the Chōkyoshinjutsu for giantification. He also utilizes telepathy for communication and tactical coordination.

In Dragon Ball Super: Broly, Piccolo's supportive role proves critical. Observing Goku's battle against Broly remotely, he telepathically communicates updates and concerns. When Goku and Vegeta retreat, they teleport to Piccolo. Recognizing fusion as the only viable strategy, Piccolo instructs the Saiyans in the precise Fusion Dance movements, correcting their errors to enable Gogeta's successful formation—instrumental in the ultimate confrontation.

Later events show Piccolo continuing his mentorship of Gohan, urging him to maintain combat readiness despite scholarly pursuits. His tactical acumen surfaces during infiltration missions against the Red Ribbon Army. After Shenron grants him a power unlock, he achieves new forms: "Ultimate Piccolo" and the enhanced "Orange Piccolo," significantly increasing his strength. Protective instincts toward Gohan's family drive his actions against threats like Gamma 2 and Cell Max. During the Tournament of Power, he demonstrates considerable power growth through strategic combat and team coordination, contributing to Universe 7's victory. His proficiency in battle planning and team management remains a consistent asset to the Dragon Team across conflicts.