Raina (68 not out off 51) was dropped twice during his stay, with the veteran of the shortest format of cricket making the most of his lives to notch up his 29th fifty in the IPL.
Raina also surpassed India and Royal Challengers Bangalore captain (RCB) captain Virat Kohli as the highest run getter in the T20 league.
Karthik (47 off 25) continued his purple patch with the bat with a well paced 47 off 25 balls where the Tamil Nadu batsman spanked medium pacer Chris Woakes in the penultimate over as the Englishman had a forgettable debut. The partnership between the pair for the fourth wicket was 87 runs.
In the last four overs, KKR leaked 54 runs at the Saurashtra Cricket Association Stadium.
Left-arm wrist spinner Kuldeep Yadav returned best figures of 2/25 in his four overs for the visitors.
Put into bat first, Gujarat Lions lost Jason Roy early on. Trying to pull Piyush Chawla, the England opener holed out to Yusuf Pathan at square leg with the ball taking the leading edge.
There was no stopping fellow opening batsman Brendon McCullum at the other end though as skipper Raina joined him at the crease.
The big hitting New Zealand batsman took a liking to Sunil Narine, hitting West Indian for three fours in his first two overs.
At the other end, Raina -- just out of BCCI a contract -- spoiled Woakes' debut for Kolkata, taking the England pacer for 18 runs.
The hosts, who finished top of the league table last year, reached 50 inside the Powerplay with Raina dropped by Kuldeep in the sixth over off Woakes.
The chinaman spinner, who recently returned first innings figures of 4/68 for India in the fourth Test against Australia, made amends soon though, taking the wicket of McCullum (35 off 24) who was plumb in front from a straight one.
Aaron Finch (15 off 8) did not last long, Kuldeep getting his second scalp inside two overs with a tossed-up googly that the Australian tried to tonk for a maximum but fell to Surya Kumar Yadav at wide long on.
Raina rode his luck in the middle, taking the aerial route more often than not and the ball somehow never finding a fielder underneath it.
The visitors had a glorious chance to break the partnership between Karthik and Raina but Kuldeep endured a brain freeze as he failed to throw the ball at the stumps with the batsman well short of his crease and wicketkeeper Robin Uthappa yelling at him.
The southpaw, who won the 2011 World Cup, brought up his half century with an on drive, soon to be grassed for the second time in the innings by Pathan off Chawla.