Captain Virat Kohli has said India could make several changes for the sixth and final ODI against South Africa, live on Sky Sports Cricket on Friday.
India - now top of the one-day rankings - sealed their first ODI series success in South Africa on Tuesday when they won by 73 runs in Port Elizabeth to take a 4-1 lead.
The tourists could stamp their dominance even further with a potential 5-1 win over the team that was ranked world No 1 at the start of the series.
With the series won, using only 12 of India's 17-man squad, Kohli said: "We want to win 5-1 but there might be a scenario to give a few (other) guys a chance.
"After this series is wrapped up we'll sit down and think about where to improve."
South Africa have so far failed to deal with the combined threat of India's two wrist spinners Yuzvendra Chahal and Kuldeep Yadav, who have taken 30 wickets between them in the series.
The Proteas had won 17 straight ODIs at home before India swept to a 3-0 lead and although they pulled one back in the rain-affected clash, even the return of AB de Villiers from injury could not save the hosts from series defeat.
Head coach Ottis Gibson said the gulf between the teams was a fair reflection of their respective abilities to score big runs.
"In every game one of their top three has scored a hundred and that's been the difference in the series," he reflected.
"We've got one hundred and when you look at the series those are the differences. Hash (Hashim Amla) has got 27 hundreds in one-day cricket so he knows how to do it, but he's not been allowed to either by the way they have bowled or the lack of confidence in our batting.
He added: "When I came here we spoke about building for the World Cup. In England in May and June I don't believe that the ball will spin as much as we've seen here.
"I think India has two world-class spinners and they might spin it anywhere, but we've got a whole year to learn to deal with that stuff. But I don't believe it will spin that much in England next year."
Seamer Kagiso Rabada was fined and slapped with one demerit point after giving India's Shikhar Dhawan a send-off during Tuesday's fifth ODI in Port Elizabeth.
Watch the sixth and final ODI between South Africa and India live on Sky Sports Cricket from 10.55am on Friday.